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Topic Review
Anti-RAS-p21 Peptides from Expression Libraries
X-ray crystallographic structures of wild-type and oncogenic RAS-p21 bound to GDP and GTP suggested that there is an absence of surface-exposed clefts to which drug molecules can bind, suggesting that RAS-p21 may be “undruggable”. This impression has proved false by a series of studies that have resulted in a number of cyclic peptides and small molecules that bind to mutant RAS-p21 proteins in their switch 2 domains in a binding “pocket” involving the switch 2 loop (residues 55–67) and the α-2 helix (residues 67–73). This binding is very much dependent on the specific amino acid substitutions that occur. When these agents bind, they strongly inhibit either GTP-bound RAS-p21 or GDP-RAS-p21. In the former case, GTP-bound RAS-p21 cannot bind to the RBD of ras, and in the latter case, GDP-bound RAS-p21 is “frozen” in an inactivated state such that it cannot exchange GDP for GTP and, since it cannot bind to GTP, it cannot adopt an activated conformation in which it presumably interacts with RAF.
  • 977
  • 29 May 2023
Topic Review
Proteomics in CSF of AD
The fact that cerebrospinal fluid (CSF) deeply irrigates the brain together with the relative simplicity of sample extraction from patients make this biological fluid the best target for biomarker discovery in neurodegenerative diseases. Biomarker discovery has been especially fruitful for the identification new proteins that appear in the CSF of Alzheimer’s disease (AD) patients together with amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau). Thus, several proteins have been already stablished as important biomarkers, due to an increase (i.e., CHI3L1) or a decrease (i.e., VGF) in AD patients’ CSF. Notwithstanding this, only a deep analysis of a database generated with all the changes observed in CSF across multiple proteomic studies, and especially those using state-of-the-art methodologies, may expose those components or metabolic pathways disrupted at different levels in AD. Deep comparative analysis of all the up- and down-regulated proteins across these studies revealed that 66% of the most consistent protein changes in CSF correspond to intracellular proteins.
  • 976
  • 08 Oct 2021
Topic Review
HIF2α/ARNT Expression for Ischemic Heart Disease Therapy
Ischemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated in response to low oxygen levels, playing crucial roles in various pathophysiological processes related to cardiovascular diseases.
  • 976
  • 26 Jul 2023
Topic Review
ADGRG1/GPR56 in Tumor Progression
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. 
  • 976
  • 16 Dec 2021
Topic Review
Hippophae rhamnoides/Cassia fistula Extracts
The work deals with the in vitro evaluations of the pod extracts of C. fistula which are shown to exert better antioxidant and enzymatic properties than those exhibited by the fruit extract of H. rhamnoides.
  • 975
  • 03 Nov 2020
Topic Review
Biomarkers of Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory disease that is very complex and heterogeneous. If not adequately treated, RA patients are likely to manifest excess of morbidity and disability with an important impact on the quality of life. Pharmacological treatment is based on the administration of the disease-modifying antirheumatic drugs (DMARDs), subdivided into conventional synthetic (csDMARDs), targeted synthetic (tsDMARDs), and biological (bDMARDs). bDMARDs are now frequently administered in patients, both as alternative treatment and together with csDMARDs. Unfortunately, there is a therapeutic response variability both to old and new drugs. 
  • 975
  • 17 Feb 2021
Topic Review
Effects of Ellagic Acid in Neurological Diseases
Aging is associated with several diseases that threaten the health of older people, such as neurodegenerative diseases, which cause indelible and irreversible damage to both the physical and psychological well-being of older people and impose a heavy burden on their families and society. In recent years, a large number of studies have focused on the therapeutic effects of Ellagic Acid, demonstrating the health benefits of EA for neurodegenerative diseases. Three common neurological diseases are described here: AD, PD, and cerebral ischemia as well as the antioxidative and anti-inflammatory protective effects of EA.
  • 975
  • 26 Oct 2022
Topic Review
Microglial Phagocytosis
       Multiple sclerosis (MS) is the most common autoimmune and demyelinating disease of the central nervous system (CNS), characterized, in the majority of cases, by initial relapses that later evolve into progressive neurodegeneration, severely impacting patients’ motor and cognitive functions. Despite the availability of immunomodulatory therapies effective to reduce relapse rate and slow disease progression, they all failed to restore CNS myelin that is necessary for MS full recovery. Microglia are the primary inflammatory cells present in MS lesions, therefore strongly contributing to demyelination and lesion extension. Thus, many microglial-based therapeutic strategies have been focused on the suppression of microglial pro-inflammatory phenotype and neurodegenerative state to reduce disease severity.
  • 974
  • 25 Aug 2020
Topic Review
COVID-19 Vaccine Approved for Public Use
Coronavirus disease 2019 (COVID-19) outbreak was first reported in Wuhan, China in December 2019, and was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel pleomorphic, positive-stranded RNA virus belonging to the Coronaviridae family. Quickly, it has become a global pandemic, infecting more than 176 million people and causing the death of more than 3.8 million individuals, that we are yet to recover from. Thus, an ongoing quest is being carried out for prophylaxis/therapy to prevent the transition from infection into serious forms of COVID-19.
  • 974
  • 30 Nov 2021
Topic Review
Applications of Antimicrobial Photodynamic Therapy
Originally discovered as a relatively new anticancer therapeutic technology, photodynamic therapy (PDT) has since evolved and is now used in many therapeutic technologies. For example, it is used against viruses, such as the recently reported antiviral activity against COVID-19, bacteria, fungi, and parasites, in treating neovascular disease, in environmental sanitation and pest control, and in many other applications. 
  • 974
  • 13 Apr 2022
Topic Review
Drug-Induced Liver Injury Assessment by Metabolomics
Drug-induced liver injury (DILI) is one of the most frequent adverse clinical reactions and a relevant cause of morbidity and mortality. Hepatotoxicity is among the major reasons for drug withdrawal during post-market and late development stages, representing a major concern to the pharmaceutical industry. The biochemical parameters for the detection of DILI are based on enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyl transpeptidase (GGT), alkaline phosphatase (ALP)) and bilirubin serum levels that are not specific of DILI and therefore there is an increasing interest on novel, specific, DILI biomarkers discovery. Metabolomics has emerged as a tool with a great potential for biomarker discovery, especially in disease diagnosis, and assessment of drug toxicity or efficacy.
  • 974
  • 07 Jul 2022
Topic Review
Bilayer Lipid Membranes in Ion Channel Functions Analysis
The bilayer lipid membrane (BLM) is the main structural component of cell membranes, in which various membrane proteins are embedded. Artificially formed BLMs have been used as a platform in studies of the functions of membrane proteins, including various ion channels. 
  • 974
  • 26 Oct 2022
Topic Review
Subclinical Acute Kidney Injury in Patients with COVID-19
Since the outbreak of COVID-19 disease, a bidirectional interaction between kidney disease and the progression of COVID-19 has been demonstrated. Kidney disease is an independent risk factor for mortality of patients with COVID-19 as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with COVID-19. However, the detection of kidney damage in patients with COVID-19 may not occur until an advanced stage based on the current clinical blood and urinary examinations. Some studies have pointed out the development of subclinical acute kidney injury (subAKI) syndrome with COVID-19. This syndrome is characterized by significant tubule interstitial injury without changes in the estimated glomerular filtration rate. Despite the complexity of the mechanism(s) underlying the development of subAKI, the involvement of changes in the protein endocytosis machinery in proximal tubule (PT) epithelial cells (PTECs) has been proposed.
  • 974
  • 29 Nov 2022
Topic Review
Therapeutic Potential of Polyphenols of Marine Origin
Polyphenols are compounds found in various plants and foods, known for their antioxidant and anti-inflammatory properties. These compounds have unique chemical structures and exhibit diverse biological properties, including anti-inflammatory, antioxidant, antimicrobial and antitumor action. Due to these properties, marine polyphenols are being investigated as possible therapeutic agents for the treatment of a wide variety of conditions, such as cardiovascular disease, diabetes, neurodegenerative diseases and cancer. 
  • 974
  • 29 May 2023
Topic Review
CFTR Lifecycle Map
Cystic Fibrosis (CF) is one of the most common genetic diseases prevalent among the Caucasian population and is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, several hundred disease-causing mutations are known, resulting in a vast range of geno- and phenotypes, which makes the development of therapeutics especially challenging. To support the development of novel therapeutics, systems biological disease maps can be used. Disease maps represent existing knowledge on disease mechanisms in a computationally readable and comprehensive manner so they can then be used by clinicians and experimental scientists as well as computational scientists for different purposes, such as structuring high-throughput data, identifying disease biomarkers, developing better diagnostics and also identifying potential drug targets and drug repositioning. The CFTR Lifecycle Map in particular details the biogenesis of CFTR in cells to support ongoing drug discovery endeavours in CF research.
  • 971
  • 22 Nov 2021
Topic Review
Hematopoietic Stem Cells and Metabolic Program
Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate (ATP), which is necessary for various cellular functions. The metabolic programs of tissue stem/progenitor cells and their underlying molecular mechanisms have been elucidated using a variety of metabolic analysis methods.
  • 971
  • 05 Jan 2023
Topic Review
Membrane Disruption Properties of EOs
Essential oils (EOs) is new possible weapons to fight antimicrobial resistance due to their inherent antimicrobial properties. However, the potential pharmaceutical use of EOs is confronted by several limitations, including being non-specific in terms of drug targeting, possessing a high cytotoxicity as well as posing a high risk for causing skin irritation.
  • 970
  • 22 Apr 2021
Topic Review
Pathophysiology of Nitrergic Enteric Neurons
Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. 
  • 970
  • 23 Jun 2021
Topic Review
MicroRNAs
In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection.
  • 970
  • 13 May 2022
Topic Review
Ceramide/Sphingosine 1-Phosphate Axis
Alzheimer’s disease (AD) is considered the most prevalent neurodegenerative disease and the leading cause of dementia worldwide. Sphingolipids, such as ceramide or sphingosine 1-phosphate, are bioactive molecules implicated in structural and signaling functions. Metabolic dysfunction in the highly conserved pathways to produce sphingolipids may lead to or be a consequence of an underlying disease.
  • 970
  • 23 Feb 2023
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