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Topic Review
Gas6/TAM Axis Involvement in COVID-19 Patients
Gas6 (growth arrest-specific gene 6) is a widely expressed vitamin K-dependent protein that is involved in many biological processes such as homeostatic regulation, inflammation and repair/fibrotic processes. It is known that it is the main ligand of TAMs, a tyrosine kinase receptor family of three members, namely MerTK, Tyro-3 and Axl, for which it displays the highest affinity. Gas6/TAM axis activation is known to be involved in modulating inflammatory responses as well as fibrotic evolution in many different pathological conditions. The Axl is a SARS-CoV-2 infection driver, the use of existing Axl inhibitors is beneficial for COVID-19 management. 
  • 801
  • 12 Jan 2023
Topic Review
Extracellular Vesicles as Novel Treatments
Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair.
  • 800
  • 14 Oct 2021
Topic Review
Inflammation Enhances the Efficacy of CFTR Modulator Therapy
The cystic fibrosis lung is inflamed and therefore the impact of inflammation on CFTR rescue should be considered. There is now evidence that airway inflammation enhances CFTR rescue. The development of CFTR modulators, such as correctors that augment F508del CFTR transfer to the apical membrane, and potentiators that increase CFTR channel activity, permitted successful treatment of the basic defect in cystic fibrosis. The first FDA-approved CFTR modulator was the potentiator ivacaftor (VX-770), which improves the function of the gating mutant G551D CFTR. While the potentiator VX-770 or the CFTR corrector lumacaftor (VX-809) alone did not significantly improve lung function in F508del CF patients, combining VX-809 with VX-770 (in the drug Orkambi) or combining the newer corrector tezacaftor (VX-661) with VX-770 (in the drug Symdeko) resulted in modest lung function improvements in clinical trials in patients homozygous for F508del CFTR. Notably, F508del rescue resulting from these combination therapies or the clinically effective novel triple therapy (in the drug Trikafta) were enhanced by airway epithelial inflammation in vitro. Thus, the airway inflammatory milieu improves the efficacy of CFTR modulators.
  • 800
  • 01 Dec 2021
Topic Review
Interleukin-18 Binding Protein Autoimmune Diseases
Natural soluble antagonist and decoy receptor on the surface of the cell membrane are evolving as crucial immune system regulators as these molecules are capable of recognizing, binding, and neutralizing (so-called inhibitors) their targeted ligands. Eventually, these soluble antagonists and decoy receptors terminate signaling by prohibiting ligands from connecting to their receptors on the surface of cell membrane. Interleukin-18 binding protein (IL-18BP) participates in regulating both Th1 and Th2 cytokines. IL-18BP is a soluble neutralizing protein belonging to the immunoglobulin (Ig) superfamily as it harbors a single Ig domain. The Ig domain is essential for its binding to the IL-18 ligand and holds partial homology to the IL-1 receptor 2 (IL-1R2) known as a decoy receptor of IL-1α and IL-1β. IL-18BP was defined as a unique soluble IL-18BP that is distinct from IL-18Rα and IL-18Rβ chain. IL-18BP is encoded by a separated gene, contains 8 exons, and is located at chr.11 q13.4 within the human genome.
  • 799
  • 08 Aug 2022
Topic Review
CADD Methods in Development of Rat Sarcoma Inhibitors
Computer-aided drug design (CADD) has been increasingly important for the discovery of new inhibitors targeting Rat Sarcoma (RAS) and its upstream or downstream signaling pathways. Based on high-resolution 3D apo or complex structures of RAS and its upstream and downstream proteins, structure-based CADD (SB-CADD) is the optimal strategy for successful inhibitor discovery, especially virtual high-throughput screening (vHTS) in combination with molecular docking and molecular dynamics (MD) simulations. In addition, ligand-based CADD (LB-CADD) is also an essential strategy for inhibitor discovery that includes quantitative structure–activity relationship (QSAR) and pharmacophore modeling. More advanced computer algorithms, such as machine learning, are also promising for the discovery of RAS-related inhibitors.
  • 797
  • 16 Sep 2022
Topic Review
Biochemical Monitoring of Aortic Aneurysm Disease
Aortic aneurysm (AA) disease is intractable. There are many different subtypes which may or may not include a genetic component. The pathology is different based on aneurysm location. Environmental factors, co-morbidities, and sex all differentially affect aneurysm formation and progression. Despite advancements in the understanding of the complex pathobiology of AAs, no efficient method for monitoring exists, and it is becoming clear that no single diagnostic approach will begin to address the many disparate pathological consequences.
  • 796
  • 07 Feb 2024
Topic Review
Biomonitoring in Occupational Exposure to Glyphosate
Glyphosate, also known under its IUPAC name N-(phosphonomethyl) glycine, while discovered by a Swiss chemist, Dr. Henri Martin, was initially developed as a chemical chelating agent, a chemical intermediate for the synthesis of other molecules, and as a possible bioactive compound.
  • 795
  • 28 Feb 2023
Topic Review
Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy
Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs) seem to be one of the central mediators of the therapeutic functions of MSCs. MSC-EVs are membrane structures secreted by the MSCs, rich in specific proteins, lipids, and nucleic acids. Amongst these, microRNAs have achieved the most attention. Unmodified MSC-EVs can promote or inhibit tumor growth, while modified MSC-EVs are involved in the suppression of cancer progression via the delivery of therapeutic molecules, including miRNAs, specific siRNAs, or suicide RNAs, as well as chemotherapeutic drugs. 
  • 795
  • 29 May 2023
Topic Review
Polymer-Based Nanosystem Strategies in Antifungal Drug Delivery
Nanosystems-based antifungal agents have emerged as an effective strategy to address issues related to drug resistance, drug release, and toxicity. Among the diverse materials employed for antifungal drug delivery, polymers, including polysaccharides, proteins, and polyesters, have gained significant attention due to their versatility. Considering the complex nature of fungal infections and their varying sites, it is crucial for researchers to carefully select appropriate polymers based on specific scenarios when designing antifungal agent delivery nanosystems. 
  • 795
  • 06 Jul 2023
Topic Review
3D Printing in Complex Medical Procedures
Medicine is a rapidly-evolving discipline, with progress picking up pace with each passing decade. This constant evolution results in the introduction of new tools and methods, which in turn occasionally leads to paradigm shifts across the affected medical fields. The following review attempts to showcase how 3D printing has begun to reshape and improve processes across various medical specialties and where it has the potential to make a significant impact. 
  • 794
  • 18 Mar 2022
Topic Review
Exhaled Aldehydes as Biomarkers for Lung Diseases
Straight-chain aliphatic aldehydes were repeatedly detected in the breath of patients suffering from lung diseases using a variety of methods, such as mass spectrometry, ion mobility spectrometry, or electro-chemical sensors.
  • 793
  • 15 Sep 2022
Topic Review
Phage-Based Therapeutics for Multi-Drug Resistant Acinetobacter baumannii
Acinetobacter baumannii is an important opportunistic human pathogen, representing one of the most challenging hospital-acquired pathogens worldwide, causing nosocomial infections, including bacteraemia, skin and soft tissue infections, wound infections, urinary tract infections, meningitis, endocarditis, and pneumonia. A. baumannii has a strong ability to form biofilms—a bacterial community enclosed in a matrix of self-produced extracellular polysaccharides that enables attachment to hospital medical equipment and surfaces, indeed, infections associated with the biofilms attached to surfaces are comparatively more difficult to treat. Phage therapy become a hot research field worldwide again after the post-antibiotic era. 
  • 792
  • 09 Feb 2023
Topic Review
Mesenchymal Stem Cells as Vehicles for Drug Delivery
Mesenchymal stem cells (MSCs) have a high tropism for the hypoxic microenvironment of tumors. The combination of nanoparticles in MSCs decreases tumor growth in vitro as well as in rodent models of cancers in vivo. Covalent conjugation of nanoparticles with the surface of MSCs can significantly increase the drug load delivery in tumor sites. Nanoparticle-based anti-angiogenic systems (gold, silica and silicates, diamond, silver, and copper) prevented tumor growth in vitro. For example, glycolic acid polyconjugates enhance nanoparticle drug delivery and have been reported in human MSCs. Labeling with fluorescent particles (coumarin-6 dye) identified tumor cells using fluorescence emission in tissues; the conjugation of different types of nanoparticles in MSCs ensured success and feasibility by tracking the migration and its intratumor detection using non-invasive imaging techniques. 
  • 790
  • 20 Nov 2023
Topic Review
Pathogenesis of Type 1 Diabetes
Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease of pancreatic β-cells, with the possible interplay of antiviral responses and other environmental factors on top of the genetic susceptibility. This ultimately leads to an aberrant β-cell stress response and the immune-mediated destruction of β-cells in the pancreata of predisposed individuals.
  • 789
  • 11 May 2022
Topic Review
Pathological Mechanisms of Mitochondria in Brain Disease
Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated in the pathogenesis of various brain diseases, including neurodegenerative disorders, stroke, and psychiatric illnesses.
  • 789
  • 24 Oct 2023
Topic Review
Therapeutic Potential of Orally Administered Rubiscolin-6
Rubiscolins are naturally occurring opioid peptides derived from the enzymatic digestion of the ribulose bisphosphate carboxylase/oxygenase protein in spinach leaves. They are classified into two subtypes based on amino acid sequence, namely rubiscolin-5 and rubiscolin-6. In vitro studies have determined rubiscolins as G protein-biased delta-opioid receptor agonists, and in vivo studies have demonstrated that they exert several beneficial effects via the central nervous system. The most unique and attractive advantage of rubiscolin-6 over other oligopeptides is its oral availability. Therefore, it can be considered a promising candidate for the development of a novel and safe drug.
  • 788
  • 25 Jun 2023
Topic Review
Machine Learning Algorithms in Developing CNS Biomarkers
Drawing from an extensive review of 66 publications, a comprehensive overview of the diverse approaches to creating mHealth-based biomarkers using machine learning is presented herein. By exploring the current landscape of biomarker development using mHealth technologies and machine learning, researchers aim to provide valuable insights into this rapidly evolving field. By doing so, researchers reflect on current challenges in this field and propose recommendations for ensuring the development of accurate, reliable, and interpretable biomarkers.
  • 787
  • 08 Jun 2023
Topic Review
Passive Immunization Strategies in Animal Models
Alpha-synucleinopathies are progressive neurodegenerative diseases that are characterized by pathological misfolding and accumulation of the protein alpha-synuclein (αsyn) in neurons, axons or glial cells in the brain, but also in other organs. The abnormal accumulation and propagation of pathogenic αsyn across the autonomic connectome is associated with progressive loss of neurons in the brain and peripheral organs, resulting in motor and non-motor symptoms. To date, no cure is available for synucleinopathies, and therapy is limited to symptomatic treatment of motor and non-motor symptoms upon diagnosis. Recent advances using passive immunization that target different αsyn structures show great potential to block disease progression in rodent studies of synucleinopathies. However, passive immunotherapy in clinical trials has been proven safe but less effective than in preclinical conditions. 
  • 786
  • 21 Feb 2022
Topic Review
Genetic Contributions to the Development of Fibromyalgia
Fibromyalgia (FM) is a centrally and peripherally mediated chronic pain syndrome with biological, psychological, and environmental predispositions. It is estimated that the prevalence of FM in the general population is 2%. FM is characterized by generalized chronic pain, fatigue, sleep changes, decreased cognitive function, and numerous tender points throughout the body. Diagnosing and treating FM are challenging. FM has a high comorbidity rate with rheumatologic disorders such as psoriatic arthritis and ankylosing spondylitis. Many FM individuals have psychiatric disorders.
  • 786
  • 12 Apr 2023
Topic Review
Dysregulation of mir-106a in Non-Cancer Diseases
MicroRNAs (miRNAs) comprise a class of non-coding RNA with extensive regulatory functions within cells. MiR-106a is recognized for its super-regulatory roles in vital processes. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that control gene expression at the translation and even transcription levels. miRNAs are critical regulators of biological processes, including cellular proliferation, differentiation, development, apoptosis, and modulation of the host response to viral infection.
  • 783
  • 03 Aug 2023
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