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International Wound Journal Aug 2023Ozone is a highly reactive oxidant molecule consisting of triatomic oxygen atoms. Ozone therapy can be achieved using ozonated hydrotherapy, ozonated oil, ozone... (Review)
Review
Ozone is a highly reactive oxidant molecule consisting of triatomic oxygen atoms. Ozone therapy can be achieved using ozonated hydrotherapy, ozonated oil, ozone autohemotherapy, and other innovative dosage forms of ozone products. Ozone is frequently used as a complementary therapy for various cutaneous diseases, including infectious skin diseases, wound healing, eczema, dermatitis, psoriasis, axillary osmidrosis, diabetic foot, and pressure ulcers. In addition, several studies have reported the superior potential of ozone therapy for improving skin and gut microbiomes, as well as antitumour and antiaging treatment. Ozone therapy is an emerging treatment strategy that acts via complex mechanisms, including antioxidant effects, immunomodulatory capacity, and modulation of local microcirculation. Studies assessing the mechanism of ozone have gradually expanded in recent years. This review article aims to summarise and explore the possible molecular biological mechanisms of ozone in cutaneous diseases and provide compelling theoretical evidence for the application of ozone in cutaneous diseases.
Topics: Humans; Skin Diseases; Skin; Ozone; Wound Healing; Skin Diseases, Infectious
PubMed: 36527235
DOI: 10.1111/iwj.14060 -
Frontiers in Medicine 2023Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the... (Review)
Review
Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of "hemodynamic coherence," i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis.
PubMed: 37476612
DOI: 10.3389/fmed.2023.1212321 -
Redox Biology Nov 2023Microvascular endothelial damage caused by intestinal ischemia‒reperfusion (II/R) is a primary catalyst for microcirculation dysfunction and enterogenous infection....
Microvascular endothelial damage caused by intestinal ischemia‒reperfusion (II/R) is a primary catalyst for microcirculation dysfunction and enterogenous infection. Previous studies have mainly focused on how neutrophil extracellular traps (NETs) and ferroptosis cause intestinal epithelial injury, and little attention has been given to how NETs, mainly from circulatory neutrophils, affect intestinal endothelial cells during II/R. This study aimed to unravel the mechanisms through which NETs cause intestinal microvascular dysfunction. We first detected heightened local NET infiltration around the intestinal microvasculature, accompanied by increased endothelial cell ferroptosis, resulting in microcirculation dysfunction in both human and animal II/R models. However, the administration of the ferroptosis inhibitor ferrostatin-1 or the inhibition of NETs via neutrophil-specific peptidylarginine deiminase 4 (Pad4) deficiency led to positive outcomes, with reduced intestinal endothelial ferroptosis and microvascular function recovery. Moreover, RNA-seq analysis revealed a significant enrichment of mitophagy- and ferroptosis-related signaling pathways in HUVECs incubated with NETs. Mechanistically, elevated NET formation induced Fundc1 phosphorylation at Tyr18 in intestinal endothelial cells, which led to mitophagy inhibition, mitochondrial quality control imbalance, and excessive mitochondrial ROS generation and lipid peroxidation, resulting in endothelial ferroptosis and microvascular dysfunction. Nevertheless, using the mitophagy activator urolithin A or AAV-Fundc1 transfection could reverse this process and ameliorate microvascular damage. We first demonstrate that increased NETosis could result in intestinal microcirculatory dysfunction and conclude that suppressed NET formation can mitigate intestinal endothelial ferroptosis by improving Fundc1-dependent mitophagy. Targeting NETs could be a promising approach for treating II/R-induced intestinal microcirculatory dysfunction.
Topics: Animals; Humans; Extracellular Traps; Endothelial Cells; Ferroptosis; Mitophagy; Microcirculation; Neutrophils
PubMed: 37812880
DOI: 10.1016/j.redox.2023.102906 -
Cell Death & Disease Jul 2023The increase of lactate is an independent risk factor for patients with sepsis-induced acute kidney injury (SAKI). However, whether elevated lactate directly promotes...
The increase of lactate is an independent risk factor for patients with sepsis-induced acute kidney injury (SAKI). However, whether elevated lactate directly promotes SAKI and its mechanism remain unclear. Here we revealed that downregulation of the deacetylase Sirtuin 3 (SIRT3) mediated the hyperacetylation and inactivation of pyruvate dehydrogenase E1 component subunit alpha (PDHA1), resulting in lactate overproduction in renal tubular epithelial cells. We then found that the incidence of SAKI and renal replacement therapy (RRT) in septic patients with blood lactate ≥ 4 mmol/L was increased significantly, compared with those in septic patients with blood lactate < 2 mmol/L. Further in vitro and in vivo experiments showed that additional lactate administration could directly promote SAKI. Mechanistically, lactate mediated the lactylation of mitochondrial fission 1 protein (Fis1) lysine 20 (Fis1 K20la). The increase in Fis1 K20la promoted excessive mitochondrial fission and subsequently induced ATP depletion, mitochondrial reactive oxygen species (mtROS) overproduction, and mitochondrial apoptosis. In contrast, PDHA1 activation with sodium dichloroacetate (DCA) or SIRT3 overexpression decreased lactate levels and Fis1 K20la, thereby alleviating SAKI. In conclusion, our results show that PDHA1 hyperacetylation and inactivation enhance lactate overproduction, which mediates Fis1 lactylation and exacerbates SAKI. Reducing lactate levels and Fis1 lactylation attenuate SAKI.
Topics: Humans; Lactic Acid; Sirtuin 3; Acute Kidney Injury; Sepsis; Apoptosis; Mitochondrial Proteins
PubMed: 37479690
DOI: 10.1038/s41419-023-05952-4 -
Romanian Journal of Internal Medicine =... Dec 2023The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and... (Review)
Review
The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and describe the relation between the central autonomic system and cardiac function and it will be presented in this narrative review. The Stroke-Heart syndrome groups the entire spectrum of cardiac changes - clinical, ECG, echocardiographic, biological, morphological - that occur in the first 30 days from the onset of stroke, especially in the first days. Their presence significantly marks the evolution and prognosis of stroke. The damage resulted from hypothalamus-pituitary-adrenal axis activation and high catecholamine release (adrenergic storm) targets mainly the myocyte and the microcirculation.The Takotsubo syndrome and Stunned myocardium are distinct forms of neurogenic myocardial ischemia - with changes in ECG, parietal motility, and biological markers - usually reversible although evolution towards cardiac dysfunction is also possible. The concept of Stroke-Heart syndrome and the brain-heart correlation brought new scientific information regarding stress cardiomyopathy or neurogenic myocardial injury.
Topics: Humans; Takotsubo Cardiomyopathy; Myocardial Stunning; Echocardiography; Stroke; Catecholamines
PubMed: 37540842
DOI: 10.2478/rjim-2023-0020 -
The Journal of Clinical Investigation Dec 2023Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel...
Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel calcifications in peripheral tissue is well studied, but microvascular calcification in the brain remains poorly understood. Here, we report that elevated platelet-derived growth factor BB (PDGF-BB) from bone preosteoclasts contributed to cerebrovascular calcification in male mice. Aged male mice had higher serum PDGF-BB levels and a higher incidence of brain calcification compared with young mice, mainly in the thalamus. Transgenic mice with preosteoclast-specific Pdgfb overexpression exhibited elevated serum PDGF-BB levels and recapitulated age-associated thalamic calcification. Conversely, mice with preosteoclast-specific Pdgfb deletion displayed diminished age-associated thalamic calcification. In an ex vivo cerebral microvascular culture system, PDGF-BB dose-dependently promoted vascular calcification. Analysis of osteogenic gene array and single-cell RNA-Seq (scRNA-Seq) revealed that PDGF-BB upregulated multiple osteogenic differentiation genes and the phosphate transporter Slc20a1 in cerebral microvessels. Mechanistically, PDGF-BB stimulated the phosphorylation of its receptor PDGFRβ (p-PDGFRβ) and ERK (p-ERK), leading to the activation of RUNX2. This activation, in turn, induced the transcription of osteoblast differentiation genes in PCs and upregulated Slc20a1 in astrocytes. Thus, bone-derived PDGF-BB induced brain vascular calcification by activating the p-PDGFRβ/p-ERK/RUNX2 signaling cascade in cerebrovascular cells.
Topics: Animals; Male; Mice; Becaplermin; Brain; Core Binding Factor Alpha 1 Subunit; Osteogenesis; Proto-Oncogene Proteins c-sis; Receptor, Platelet-Derived Growth Factor beta; Vascular Calcification
PubMed: 37815871
DOI: 10.1172/JCI168447 -
Journal of Clinical Medicine Aug 2023Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is... (Review)
Review
Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.
PubMed: 37685660
DOI: 10.3390/jcm12175592