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Topic Review
RSU1 in Tumor Tissues
Cancer is a multifactorial disease responsible for millions of deaths worldwide. It has a strong genetic background, as mutations in oncogenes or tumor suppressor genes contribute to the initiation of cancer development. Integrin signaling as well as the signaling pathway of Ras oncogene, have been long implicated both in carcinogenesis and disease progression. Moreover, they have been involved in the promotion of metastasis, which accounts for the majority of cancer-related deaths. Ras Suppressor-1 (RSU1) was identified as a suppressor of Ras-induced transformation and was shown to localize to cell-extracellular matrix adhesions. Recent findings indicate that its expression is elevated in various cancer types, while its role in regulating metastasis-related cellular processes remains largely unknown. Interestingly, there is no in vivo work in the field to date, and thus, all relevant knowledge stems from in vitro studies.
  • 1.3K
  • 27 Oct 2020
Topic Review
HMGB1
Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Despite successful obliteration of aneurysm from the circulation, the clinical outcome of aSAH patients is often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The evidence suggested that HMGB1contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.
  • 1.3K
  • 28 Oct 2020
Topic Review
Portal Vein Thrombosis
The purpose of our study was to examine the prevalence of inherited and acquired thrombophilia in cirrhotic non-malignant portal vein thrombosis (PVT) at our center. As secondary aims we explored the influence of these disorders on the clinical presentation of PVT and response to anticoagulation. 
  • 1.3K
  • 12 Oct 2020
Topic Review
Nutrients and Porphyria
Porphyria refers to a group of fascinating diseases from a metabolic and nutritional standpoint as it provides an example of how metabolic manipulation can be used for therapeutic purposes. It is characterized by defects in heme synthesis, particularly in the erythrocytes and liver. Specific enzymes involved in heme biosynthesis directly depend on adequate levels of vitamins and minerals in the tissues. Moreover, micronutrients that are required for producing succinyl CoA and other intermediates in the Krebs (TCA) cycle are indirectly necessary for heme metabolism. This review summarizes articles that describe the nutritional status, supplements intake and dietary practices of patients affected by porphyria, paying special attention to the therapeutic use of nutrients that may help or hinder this group of diseases.
  • 1.3K
  • 28 Oct 2020
Topic Review
Phytoplasma Taxonomy
Phytoplasmas are pleomorphic, wall-less intracellular bacteria that can cause devastating diseases in a wide variety of plant species. Rapid diagnosis and precise identification of phytoplasmas responsible for emerging plant diseases are crucial to preventing further spread of the diseases and reducing economic losses. Phytoplasma taxonomy (identification, nomenclature, and classification) has lagged in comparison to culturable bacteria, largely due to lack of axenic phytoplasma culture and consequent inaccessibility of phenotypic characteristics. However, the rapid expansion of molecular techniques and the advent of high throughput genome sequencing have tremendously enhanced the nucleotide sequence-based phytoplasma taxonomy. 
  • 1.3K
  • 01 Sep 2022
Topic Review
Leptin Cellular Signaling in Brain
The triad of obesity, metabolic syndrome (MetS), Type 2 diabetes mellitus (T2DM) and advancing age are currently global societal problems that are expected to grow over the coming decades. This triad is associated with multiple end-organ complications of diabetic vasculopathy (maco-microvessel disease), neuropathy, retinopathy, nephropathy, cardiomyopathy, cognopathy encephalopathy and/or late-onset Alzheimer’s disease. 
  • 1.3K
  • 01 Jun 2021
Topic Review
Central Vein Sign in MS
Magnetic resonance imaging (MRI) is the most important paraclinical support in multiple sclerosis (MS) diagnostic work-up. Still, its specificity using conventional sequences is limited as the cerebral white matter (WM) findings in patients with different morbidities may be mistakenly interpreted as MS lesions. Therefore, more MS-specific MRI criteria to rule out disorders are needed. The central vein sign (CVS) has been proposed as an MS imaging biomarker to differentiate MS from MS-radiological mimicking disorders, implementing susceptibility-based MRI sequences. In this study, we aim to systematically review the proportion of MS  lesions which show the CVS and estimate the performance diagnostic value in discriminating MS from its common radiological differential diagnosis. Also, we investigate the impact of using different magnetic field strengths, specific sequences and post-processing techniques.
  • 1.3K
  • 10 Dec 2020
Topic Review
Muscle Proteolysis and Autophagy
Several pathophysiological mechanisms such as oxidative stress, systemic inflammation, increased proteolysis, autophagy and apoptosis, and signaling pathways were shown to be involved in the process of muscle mass loss in limb muscles of cachectic patients with chronic conditions and in animal models. Whether prolonged periods of immobilization may impair to a greater extent the muscle mass loss and dysfunction elicited by cancer-induced cachexia needs to be further investigated. Investigation of to what extent each particular condition: either cancer cachexia or prolonged immobilization contributes to the wasting process of muscle mass also remains to be clarified. 
  • 1.3K
  • 10 Nov 2020
Topic Review
Skeletal Muscle Extracellular Matrix
The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes, and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.
  • 1.3K
  • 09 Sep 2021
Topic Review
Treatment of Sjogren’s Syndrome
This entry summarizes the current knowledge of T cells subsets contribution to the SS immunopathology, focusing on the cellular and biomolecular properties allowing them to infiltrate and to harm target tissues and, that simultaneously make them key therapeutic targets for SS treatment. 
  • 1.3K
  • 18 Nov 2020
Topic Review
KRAS in Pancreatic Adenocarcinoma Microenvironment
The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). 
  • 1.3K
  • 13 Oct 2021
Topic Review
Citicoline in TBI Management
Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is a need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements in the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI.
  • 1.3K
  • 07 May 2021
Topic Review
Tuberculosis
Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). Thus, an understanding of the intricate pathways involved in the dendritic cell response are needed to prevent co-infections and co-morbidities in individuals with TB and HIV
  • 1.3K
  • 30 Dec 2020
Topic Review
Air Pollution Induced Disorders
Air pollution is a heterogeneous mixture of various constituents resulting from the complex interaction of multiple emissions and chemical reactions. This mixture comprises solid particles and liquid droplets suspended in the air, i.e., PM2.5, that can include organic carbon (OC), elemental or black carbon (EC), nitrates, sulfates, and metals (e.g., iron, vanadium, nickel, copper, and manganese) as well as gases (e.g., ground level ozone (O3), carbon monoxide (CO), sulfur dioxide (SO2), oxides of nitrogen (NOx)) gaseous organic compounds (e.g., non-methane volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)), bacterial endotoxins (mostly bound to solid particles or liquid aerosols). There are two possible ways by which air pollutants enter the CNS, either through direct transport of particles into the CNS or via systemic inflammation upon initial recruitment of immune cells in the lung tissue. Once in the organism, the adverse effects of fine particulates on the brain rely mainly on three mechanisms. First, they can induce the release of proinflammatory mediators leading to chronic respiratory and systemic inflammation, thereby affecting the BBB and ultimately triggering neural-immune interaction and resulting in increased production of ROS and chronic oxidative stress. Second, the particles can damage the BBB through the direct formation of ROS and thereby alter the permeability of the barrier. Third, there can be mechanical stimulation of specific mechano-receptors in pulmonary tissue leading to the lung arc reflex and sympathetic activation with the release of vasoconstrictors such as catecholamines. 
  • 1.3K
  • 26 Oct 2020
Topic Review
L-Carnitine and Balanced Diet in Alzheimer’s Disease
The prevention or alleviation of neurodegenerative diseases, including Alzheimer’s disease (AD), is a challenge for contemporary health services. For the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, it contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency.
  • 1.3K
  • 16 May 2022
Topic Review
Stable Isotope Fractionation in Diseases
The natural abundance of heavy stable isotopes (13C, 15N, 18O, etc.) is now of considerable importance in many research fields, including human physiology. In fact, it varies between tissues and metabolites due to isotope effects in biological processes, that is, isotope discriminations between heavy and light isotopic forms during enzyme or transporter activity.
  • 1.3K
  • 23 Jun 2021
Topic Review
Stabilin-2 and Cancer Metastasis
Stabilin-2 is a systemic clearance receptor for hyaluronic acid (HA).  HA is typically enriched in the extracellular matrix of several types of cancer cells, thus, Stabilin-2 may interact with the extracellular matrix of cancer cells depending on the physiological environment of the tissue.  This is especially relevant for the liver sinusoids and lymph nodes which express high levels of Stabilin-2 and also are sites of metastases for a number of cancer types.
  • 1.3K
  • 28 Oct 2020
Topic Review
Endothelial Injury Syndromes
Immunotherapy with chimeric antigen receptor T (CAR-T cells) has been recently approved for patients with relapsed/refractory B-lymphoproliferative neoplasms. Along with great efficacy in patients with poor prognosis, CAR-T cells have been also linked with novel toxicities in a significant portion of patients. Cytokine release syndrome (CRS) and neurotoxicity present with unique clinical phenotypes that have not been previously observed. Nevertheless, they share similar characteristics with endothelial injury syndromes developing post hematopoietic cell transplantation (HCT). Evolution in complement therapeutics has attracted renewed interest in these life-threatening syndromes, primarily concerning transplant-associated thrombotic microangiopathy (TA-TMA). The immune system emerges as a key player not only mediating cytokine responses but potentially contributing to endothelial injury in CAR-T cell toxicity. The interplay between complement, endothelial dysfunction, hypercoagulability and inflammation seems to be a common denominator in these syndromes. As the indications for CAR-T cells and patient populations expand, there in an unmet clinical need of better understanding the pathophysiology of CAR-T cell toxicity. Therefore, this review aims to provide state-of-the art knowledge on: cellular therapies in clinical practice (indications and toxicities), endothelial injury syndromes and immunity and potential therapeutic targets.
  • 1.3K
  • 06 Nov 2020
Topic Review
CFTR Biogenesis
Cystic fibrosis (CF) is one of the most common severe autosomal recessive genetic diseases in individuals of European descent.
  • 1.3K
  • 26 May 2021
Topic Review
ISIDOG Recommendations Concerning COVID-19, Pregnancy
To properly manage pregnant patients in times of Sars-2-CoV (Covid-19) pandemics, extra knowledge, skills and organisational measures are essential. After consultation of more than 20 knowledgeble ISIDOG country responsables in Europe and worldwide, we present a comprehensive review and clear recommendation  document to guide caretakers of pregnant women in all possible aspects of the manangement.  Care of patient with, or at risk of, COVID-19 infection, requires attention to minimize the potential pathogenic effect for the mother and the offspring, but also not to spread infection to themselves, caregivers or partners. ISIDOG will adjust guidelines egularly as more information becomes available.
  • 1.3K
  • 01 Nov 2020
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