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Topic Review
Genesis of Endotheliopathy
Endotheliopathy, according to the “two-activation theory of the endothelium”, is triggered by the activated complement system in critical illnesses, such as sepsis, diabetes and polytrauma, leading to two distinctly different molecular dysfunctions: (1) the activation of the inflammatory pathway due to the release of inflammatory cytokines, such as interleukins, interferons and tumor necrosis factors, and (2) the activation of the microthrombotic pathway due to the exocytosis of hemostatic factors, including ultra-large von Willebrand factor (ULVWF) multimers and FVIII. These lead to inflammation and microthrombogenesis. The former produces inflammatory diseases, and the latter produces endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), which orchestrates not only TTP-like syndrome characterized by the triad of consumptive thrombocytopenia, microangiopathic hemolytic anemia and multiorgan dysfunction syndrome, but also many other endotheliopathic syndromes. The diagnostic features of EA-VMTD are well established now and therapeutic strategies are being formulated. 
  • 770
  • 11 Oct 2022
Topic Review
VEGF
VEGF-A (also called VEGF) is a member of the mammalian platelet-derived growth factor (PDGF) supergene family which also includes VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF).
  • 768
  • 05 May 2021
Topic Review
Primary Polydipsia
Primary polydipsia, or psychogenic polydipsia, is a form of polydipsia characterised by excessive fluid intake in the absence of physiological stimuli to drink. Psychogenic polydipsia which is caused by psychiatric disorders, often schizophrenia, is often accompanied by the sensation of dry mouth. Some forms of polydipsia are explicitly non-psychogenic. Primary polydipsia is a diagnosis of exclusion.
  • 767
  • 22 Nov 2022
Topic Review Peer Reviewed
SARS, MERS and COVID-19-Associated Renal Pathology
Coronaviruses are a large group of RNA viruses, the most notable representatives of which are SARS-CoV, MERS-CoV and SARS-CoV-2. Human coronavirus infections were first documented in the 1960s, when members causing seasonal common colds were successfully replicated in human embryonal trachea and kidney cell cultures and classified based on electron microscopy. The history of coronaviruses stretched far back to that point, however, with some representatives causing disease in animals identified several decades prior and evolutionary data pointing towards the origin of this viral group more than 55 million years ago. In the short time period of research since they were discovered, coronaviruses have shown significant diversity, genetic peculiarities and varying tropism, resulting in the three identified causative agents of severe disease in humans—SARS, MERS and the most recent one, COVID-19, which has surpassed the previous two due to causing a pandemic resulting in significant healthcare, social and political consequences. Coronaviruses are likely to have caused pandemics long before, such as the so-called Asian or Russian influenza. Despite being epitheliotropic viruses and predominantly affecting the respiratory system, these entities affect multiple systems and organs, including the kidneys. In the kidneys, they actively replicate in glomerular podocytes and epithelial cells of the tubules, resulting in acute kidney injury, seen in a significant percentage of severe and fatal cases. Furthermore, the endothelial affinity of the viruses, resulting in endotheliitis, increases the likelihood of thrombotic microangiopathy, damaging the kidneys in a two-hit mechanism. As such, recently, COVAN has been a suggested nomenclature change indicating renal involvement in coronavirus infections and its long-lasting consequences. 
  • 767
  • 10 Oct 2022
Topic Review
Ketogenic Diet for Preoperative Weight Reduction
Bariatric surgery (BS) is the most effective treatment in patients with severe obesity in terms of durable weight loss and reduction of comorbidity burden and mortality. Pre-operative weight loss can limit anesthesiological and surgical risks. Ketogenic diet (KD) is an “umbrella term” under which different low-carbohydrate dietary protocols are included. The effect of KD for preoperative weight reduction in BS is described. 
  • 766
  • 22 Sep 2022
Topic Review
Protamine-Based Strategies for RNA Transfection
Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers.
  • 768
  • 07 Jul 2021
Topic Review
Novel Selective RET Inhibitors
RET-selective tyrosine kinase inhibitors (TKIs) pralsetinib and selpercatinib, are effective against the RET V804L/M gatekeeper mutants. However, adaptive mutations that cause resistance at the solvent front RET G810 residue have been found, pointing to the need for the development of the next-generation of RET-specific TKIs. 
  • 767
  • 29 Apr 2021
Topic Review
Pharmacological Treatment in Presbyopia
Pharmacological treatment of presbyopia may be an alternative for those who want a spectacle-free scenario and an easy-to-use method with lower risk of irreversible ocular adverse events. There are two main agents, miotics and lens softeners, investigated as agents for the pharmacological treatment. Miotic agents treat presbyopia by creating a pinhole effect which may increase the depth of focus at all working distances. Lens softeners increase the elasticity of the lens, which is targeted at one of the etiologic mechanisms of presbyopia. 
  • 767
  • 14 Mar 2022
Topic Review
Marine Resources for COVID-19 Treatment
Marine resources have significant pharmacological potential in combatting various diseases, such as COVID-19. The wide variety of marine bioactive compounds and their implications are extensive. Micro and macro-organisms produce inorganic polyphosphates, sulfated polysaccharides, Bromotyrosines and many more. These compounds possess unique properties that allow them to combat Sars-Cov-2 infection, proving as efficacious potential therapeutics. Despite the challenges faced, marine organisms serve as a promising avenue for future pharmacological intervention. The present review for the first time highlights marine bioactive compounds, their sources, and their anti-viral mechanisms of action, with a focus on potential COVID-19 treatment.
  • 767
  • 27 Jul 2021
Topic Review
Therapies for Metastatic Thyroid Cancer
In this Review Article, we discuss the molecular landscape of thyroid cancer and the published and ongoing clinical studies focused on targeted therapies for advanced thyroid cancer. This article serves as a concise resource with up to date literature about this rapidly evolving field.
  • 766
  • 24 Aug 2020
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