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Topic Review
Anti-Amyloidogenic Properties of Transthyretin and Apolipoprotein E
Transthyretin (TTR) is a 55 kDa homotetrameric protein circulating in the plasma and CSF. Its main physiological function is to transport thyroid hormone thyroxine (T4) and retinol-binding protein. Apolipoprotein E (ApoE) is a 34 kDa lipid-binding and transport protein found in both serum and CSF. Amyloid formation is a pathological process associated with a wide range of degenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and diabetes mellitus type 2. During disease progression, abnormal accumulation and deposition of proteinaceous material are accompanied by tissue degradation, inflammation, and dysfunction. Agents that can interfere with the process of amyloid formation or target already formed amyloid assemblies are consequently of therapeutic interest. TTR and ApoE are among the few endogenous proteins with anti-amyloidogenic activity, therefore understanding their role and mechanism of action on amyloid formation can help in developing new therapeutic strategies. 
  • 1.3K
  • 07 May 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
Peripheral Arterial Disease (PAD)
Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation.
  • 1.3K
  • 19 Jan 2021
Topic Review
JAK/STAT in Interstitial Lung Diseases
Janus kinases (JAK) are a group of intracellular tyrosine kinases (JAK1, JAK2, JAK3, TYK2) that are crucial in signal transduction initiated by a wide range of membrane receptors. Signal transducer and activator of transcription (STAT) comprises a family of 7 members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6), which function as transcription factors. The JAK/STAT signaling pathway controls multiple cellular processes that are essential for cell homeostasis.Between the different JAK/STAT isoforms, it appears that JAK2/STAT3 are predominant, initiating cellular changes observed in ILDs.
  • 1.3K
  • 25 Jun 2021
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
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
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
SiRNA
Short interfering RNAs (siRNAs), also recognized as small RNAi, are double-stranded RNAs with 21–25 nucleotides that are applied to silence target genes in cells. siRNAs are made of two single sequences, named sense strand (passenger strand) and antisense strand (guide strand), connected by an active protein complex called the RNA-Induced Silencing Complex (RISC).
  • 1.3K
  • 18 Dec 2020
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
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
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
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
Delirium Treatment
The presentation of common acute diseases in older age is often referred to as "atypical”. Frequently, the symptom is neither single nor tissue- related. In most cases, the onset of symptoms and diseases is the expression of diminished reserve with failure of body-system, and imbalance of brain function. Delirium is one of the main devastating and prevalent atypical symptoms and could be considered as a geriatric syndrome. It is encompassing an array of neuropsychiatric symptoms and represents a disarrangement of the cerebral function in response to one or more stressors. The most recent definition, reported in the DSM-V, depicts delirium as a clear disturbance in attention and awareness. The deficit is to be developed in a relatively short time-period time (usually hours or days). The attention disorder must be associated with another cognitive impairment in memory, orientation, language, visual-spatial or perception abilities. For the treatment it is imperative remove potential causes of delirium, before prescribing drugs. Even a non-pharmacological approach to reduce precipitating causes should be identified and treated. When we are forced to approach the pharmacological treatment of hyperkinetic delirium in older persons, we should select highly cost-effective drugs. High attention should be devoted to the correct balance between improvement of psychiatric symptoms and occurrence of side-effects. Clinicians should be guided in the correct choice of drugs following cluster symptoms presentation, excluding drugs that potentially could produce complications rather than advantages. In this brief point-of-view, we propose a novel pharmacological flow-chart of treatment in relation to the basic clusters of diseases of the older patient admitted acutely to the hospital and in particular we emphasized “how should we do not do!”, with the intention of avoiding possible side effects of drugs used.
  • 1.3K
  • 29 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
LC-MS-Based Proteomic Analyses to Diagnose Infectious Diseases
Rapid and precise diagnostic methods are required to control emerging infectious diseases effectively. Body fluids are good reservoirs for infectious parasites, bacteria, and viruses. Therefore, recent clinical proteomics methods have focused on body fluids when aiming to discover human- or pathogen-originated diagnostic markers. Here, the clinical characteristics of each body fluid, recent tandem mass spectroscopy (MS/MS) data-acquisition methods, and applications of body fluids for proteomics regarding infectious diseases (including the coronavirus disease of 2019 [COVID-19]), are summarized and discussed.
  • 1.3K
  • 19 Apr 2022
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
SARS-CoV-2 Spike Protein and Cell-Signaling
The SARS-CoV-2 spike protein, a class I viral fusion protein, is critical to initiating the interactions between the virus and the host cell surface receptor, facilitating viral entry into the host cell by assisting in the fusion of the viral and host cell membranes. Human host cells also sensitively respond to the spike protein to elicit cell signaling.
  • 1.3K
  • 21 Feb 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
Spinal Sarcopenia
Spinal sarcopenia is a complex and multifactorial disorder associated with loss of strength, increased frailty, and increased risk of fractures and falls. In addition, spinal sarcopenia has been associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems—such as osteoporotic fractures and low bone mineral density—and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.
  • 1.3K
  • 29 Oct 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
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