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Topic Review
Posterior Polar Annular Choroidal Dystrophy
Posterior polar annular choroidal dystrophy (PPACD) is a rare ocular disorder and presents as symmetric degeneration of the retinal pigment epithelium (RPE) and the underlying choriocapillaris, encircling the retinal vascular arcades and optic disc. This condition distinctively preserves the foveal region, optic disc, and the outermost regions of the retina. Despite its distinct clinical presentation, due to the infrequency of its occurrence and the limited number of reported cases, the pathophysiology, and the genetic foundations of PPACD are still largely uncharted.
  • 128
  • 29 Feb 2024
Topic Review
Prenatal Melatonin in Regulation of Childhood Obesity
There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin’s effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.
  • 111
  • 29 Feb 2024
Topic Review
Tumour Microenvironment and Metabolism
Many of the factors associated with tumour progression and immune resistance, such as yin yang (YY)1 and glycogen synthase kinase (GSK)3β, regulate acetyl-CoA and the melatonergic pathway, thereby having significant impacts on the dynamic interactions of the different types of cells present in the tumour microenvironment. The association of the aryl hydrocarbon receptor (AhR) with immune suppression in the tumour microenvironment may be mediated by the AhR-induced cytochrome P450 (CYP)1b1-driven ‘backward’ conversion of melatonin to its immediate precursor N-acetylserotonin (NAS). NAS within tumours and released from tumour microenvironment cells activates the brain-derived neurotrophic factor (BDNF) receptor, TrkB, thereby increasing the survival and proliferation of cancer stem-like cells. Acetyl-CoA is a crucial co-substrate for initiation of the melatonergic pathway, as well as co-ordinating the interactions of OXPHOS and glycolysis in all cells of the tumour microenvironment. This provides a model of the tumour microenvironment that emphasises the roles of acetyl-CoA and the melatonergic pathway in shaping the dynamic intercellular metabolic interactions of the various cells within the tumour microenvironment. The potentiation of YY1 and GSK3β by O-GlcNAcylation will drive changes in metabolism in tumours and tumour microenvironment cells in association with their regulation of the melatonergic pathway. 
  • 99
  • 29 Feb 2024
Topic Review
Brain Neurodegeneration and Cognitive Deficits after Cardiac Arrest
Cardiac arrest occurs as a result of a sudden stop of the heartbeat and its mechanical activity, which causes cessation of systemic circulation and blood flow in the brain, which triggers global brain ischemia. Brain neuropathology after cardiac arrest includes primary ischemic injury and secondary reperfusion injury, which occur sequentially, acutely during cardiac arrest and resuscitation, and chronically in the post-resuscitation stag.
  • 443
  • 29 Feb 2024
Topic Review
Oxidative Stress Implications for Retinal Diseases
Oxidative stress plays a significant role in the pathogenesis of various retinal diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and retinopathy of prematurity (ROP).
  • 125
  • 29 Feb 2024
Topic Review
COVID-19 and the Kidney
The new respiratory infectious disease coronavirus disease 2019 (COVID-19) that originated in Wuhan, China, in December 2019 and caused by a new strain of zoonotic coronavirus, named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Most of the deceased patients had pre-existing comorbidities; over 20% had chronic kidney disease (CKD). Furthermore, although SARS-CoV-2 infection is characterized mainly by diffuse alveolar damage and acute respiratory failure, acute kidney injury (AKI) has developed in a high percentage of cases.
  • 91
  • 29 Feb 2024
Topic Review
Retreatment Strategies for Calcium Silicate-Based Root Canal Sealers
Since the introduction of calcium silicate-based materials in dentistry, calcium silicate-based root canal sealers have become popular among dentists because of their biocompatibility, bioactivity, and sealing ability. Therefore, effective retreatment strategies are indispensable.
  • 155
  • 29 Feb 2024
Topic Review
RA, OA, and IVL in Calcified Coronary Lesions
In order to improve the percutaneous treatment of coronary artery calcifications (CAC) before stent implantation, methods such as rotational atherectomy (RA), orbital atherectomy (OA), and coronary intravascular lithotripsy (IVL) were invented. These techniques use different mechanisms of action and therefore have various short- and long-term outcomes. IVL employs sonic waves to modify CAC, whereas RA and OA use a rapidly rotating burr or crown. These methods have specific advantages and limitations, regarding their cost-efficiency, the movement of the device, their usefulness given the individual anatomy of both the lesion and the vessel, and the risk of specified complications.
  • 182
  • 28 Feb 2024
Topic Review
Off-Target Effects of P2Y12 Receptor Inhibitors
Ischemic heart disease holds the foremost position as the primary contributor to mortality from cardiovascular disease (CVD). Furthermore, it constitutes the predominant underlying cause of heart failure on a global scale. Diverging from other tissues, the myocardium demonstrates a markedly limited ability to regenerate in the aftermath of injuries. Consequently, necrotic cardiomyocytes are replaced by fibrotic scar tissue in the cardiac repair process, which can lead to an adverse cardiac remodeling. Different cell types, including fibroblasts and macrophages, are involved in this process and play a pivotal role by releasing a wide array of mediators (i.e., cytokines) that regulate the activation of multiple molecular pathways, such as the Wnt/β-catenin pathway, involved in cardiac fibrosis. For this reason, the modulation of these pathways might be effective in promoting the replacement of fibrosis in reactive tissue. Dual antiplatelet therapy (DAPT), consisting of the combination of a platelet P2Y12 receptor inhibitor and aspirin, is the cornerstone of treatment for patients with acute coronary syndromes (ACS) requiring percutaneous coronary interventions (PCI). P2Y12 receptor activation, a platelet purinergic receptor for adenosine 5′-diphosphate (ADP), significantly contributes to the arterial thrombosis process. 
  • 201
  • 28 Feb 2024
Topic Review
Cardiovascular Management of Myotonic Dystrophy Type 1 Patients
Myotonic dystrophy is a hereditary disorder with systemic involvement. Cardiac involvement occurs in 80% of MD1 patients and it often precedes the involvement of skeletal muscle. Cardiac involvement in patients with MD1 occurs as a degenerative process, with progressive fibrosis and fatty replacement of the myocardium, which involves not only the specialized conduction system but also areas, initially unaffected, of the atrial and ventricular myocardium. This anatomy-pathologic substrate may, on the one hand, facilitate the development of cardiac conduction diseases, ventricular tachycardia (VT), and sudden cardiac death (SCD) on the other hand, it may be responsible for ventricular dyssynchrony, leading to cardiomyopathy with systolic dysfunction.
  • 585
  • 28 Feb 2024
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