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Topic Review
Autophagy in Nanomaterial Toxicity
Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.
  • 1.0K
  • 28 Oct 2020
Topic Review
Monoclonal Antibodies in Treating Inflammatory Bowel Disease
Monoclonal antibodies (MAbs) have revolutionized the treatment of many chronic inflammatory diseases, including inflammatory bowel disease (IBD). IBD is a term that comprises two quite similar, yet distinctive, disorders—Crohn’s disease (CD) and ulcerative colitis (UC). Two blockbuster MAbs, infliximab (IFX) and adalimumab (ADL), transformed the pharmacological approach of treating CD and UC. However, due to the complex interplay of pharmacology and immunology, MAbs face challenges related to their immunogenicity, effectiveness, and safety.
  • 1.0K
  • 19 Sep 2022
Topic Review
Botryllus schlosseri
Botryllus schlosseri, a colonial tunicate, which is the nearest invertebrate group to the vertebrates, is devoid of T- and B-cell-based adaptive immunity. It has unique characteristics that make it a valuable model system for studying innate immunity mechanisms: (i) a natural allogeneic transplantation phenomenon that results in either fusion or rejection; (ii) whole animal regeneration and noninflammatory resorption on a weekly basis; (iii) allogeneic resorption which is comparable to human chronic rejection. Recent studies in B. schlosseri have led to the recognition of a molecular and cellular framework underlying the innate immunity loss of tolerance to allogeneic tissues. Additionally, B. schlosseri was developed as a model for studying hematopoietic stem cell (HSC) transplantation, and it provides further insights into the similarities between the HSC niches of human and B. schlosseri. The entry is from Botryllus schlosseri as a Unique Colonial Chordate Model for the Study and Modulation of Innate Immune Activity. August 2021Marine Drugs 19(8):454. DOI: 10.3390/md19080454
  • 1.0K
  • 30 Aug 2021
Topic Review
miRNA and lncRNA Dysregulation in Diabetes
Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the ‘symptom complex’ in diabetes.
  • 1.0K
  • 02 Nov 2022
Topic Review
Histone Deacetylases
Histone acetylation status is considered a potential diagnostic biomarker for depression, while inhibitors of histone deacetylases (HDACs) have garnered interest as novel therapeutics.
  • 1.0K
  • 08 Jun 2021
Topic Review
Characterization of Sodium-Alginate-Based Hydrogels
Alginates are polysaccharides that are produced naturally and can be isolated from brown sea algae and bacteria. Sodium alginate (SA) is utilized extensively in the field of biological soft tissue repair and regeneration owing to its low cost, high biological compatibility, and quick and moderate crosslinking.
  • 1.0K
  • 14 Aug 2023
Topic Review
Lipids for Renal Cell Carcinoma Therapy
Kidney cancer is among the top ten most common cancers to date. Within the kidney, renal cell carcinoma (RCC) is the most common solid lesion occurring. Mutations in the von Hippel–Lindau gene (Vhl) have attracted a lot of interest since this gene regulates the hypoxia inducible transcription factors HIF-1α and HIF-2α, which in turn drive the transcription of many genes that are important for renal cancer growth and progression, including genes involved in lipid metabolism and signaling.
  • 1.0K
  • 08 Mar 2023
Topic Review
Proteomic Research on Antitumor Properties of Medicinal Mushrooms
Medicinal mushrooms are increasingly being recognized as an important therapeutic modality in complementary oncology. Until now, more than 800 mushroom species have been known to possess significant pharmacological properties, of which antitumor and immunomodulatory properties have been the most researched. Besides a number of medicinal mushroom preparations being used as dietary supplements and nutraceuticals, several isolates from mushrooms have been used as official antitumor drugs in clinical settings for several decades. Various proteomic approaches allow for the identification of a large number of differentially regulated proteins serendipitously, thereby providing an important platform for a discovery of new potential therapeutic targets and approaches as well as biomarkers of malignant disease. This entry is focused on the current state of proteomic research into antitumor mechanisms of some of the most researched medicinal mushroom species, including Phellinus linteus, Ganoderma lucidum, Auricularia auricula, Agrocybe aegerita, Grifola frondosa, and Lentinus edodes, as whole body extracts or various isolates, as well as of complex extract mixtures.
  • 1.0K
  • 15 Nov 2021
Topic Review
Vitamin K Antagonists
The efficacy and safety of vitamin K antagonists (VKAs) as oral anticoagulants (OACs) depend on the quality of anticoagulation control, as reflected by the mean time in therapeutic range (TTR). 
  • 1.0K
  • 12 Apr 2021
Topic Review
Mechanisms of Neurorespiratory Toxicity Induced by Fentanyl Analogs
In 2020, fentanyl and its analogs contributed to ~65% of drug-attributed fatalities in the USA, with a threatening increasing trend during the last ten years. These synthetic opioids used as potent analgesics in human and veterinary medicine have been diverted to recreational aims, illegally produced and sold. Like all opioids, central nervous system depression resulting from overdose or misuse of fentanyl analogs is characterized clinically by the onset of consciousness impairment, pinpoint miosis and bradypnea. However, contrasting with what observed with most opioids, thoracic rigidity may occur rapidly with fentanyl analogs, contributing to increasing the risk of death in the absence of immediate life support. Various mechanisms have been proposed to explain this particularity associated with fentanyl analogs, including the activation of noradrenergic and glutamatergic coerulospinal neurons and dopaminergic basal ganglia neurons. Due to the high affinities to the mu-opioid receptor, the need for more elevated naloxone doses than usually required in morphine overdose to reverse the neurorespiratory depression induced by fentanyl analogs has been questioned. 
  • 1.0K
  • 03 May 2023
Topic Review
Developments on 14-Oxygenated-N-methylmorphinan-6-ones
Adequate pain management, particularly chronic pain, remains a major challenge associated with modern-day medicine. Current pharmacotherapy offers unsatisfactory long-term solutions due to serious side effects related to the chronic administration of analgesic drugs. Morphine and structurally related derivatives (e.g., oxycodone, oxymorphone, buprenorphine) are highly effective opioid analgesics, mediating their effects via the activation of opioid receptors, with the mu-opioid receptor subtype as the primary molecular target. However, they also cause addiction and overdose deaths, which has led to a global opioid crisis in the last decades. Therefore, research efforts are needed to overcome the limitations of present pain therapies with the aim to improve treatment efficacy and to reduce complications.
  • 1.0K
  • 30 Sep 2021
Topic Review
Fexinidazole: All-Oral Therapy for Human African Trypanosomiasis
Human African trypanosomiasis (HAT or ‘sleeping sickness’) is a neglected tropical disease. If untreated, it is always fatal and leads to death. A few treatments are available for HAT, but most of them require a skilled professional, which increases the financial burden on the patient. Recently, fexinidazole (FEX) has been approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of stage-1 (hemolymphatic) as well as stage-2 (meningoencephalitic) of HAT. Before the FEX approval, there were separate treatments for stage-1 and stage-2 of HAT. 
  • 1.0K
  • 25 Jan 2022
Topic Review
Agrimonolide from Agrimonia pilosa Ledeb.
Agrimonolide (AM), which is a derivative of isocoumarins, is found mainly in the herb Agrimonia pilosa Ledeb. This compound is highly lipophilic and readily crosses the blood–brain barrier. Interest has grown in the use of AM as a multitarget natural treatment for various diseases, such as cancer, inflammation, hepatic injury, myocardial damage, and diabetes mellitus. The potential mechanisms of these pharmacological effects have been clarified at cellular and molecular levels. AM shows no cytotoxicity over a range of concentrations in different types of cells, providing evidence for its good safety profile in vitro. These findings indicate that AM is a promising medicinal agent.
  • 1.0K
  • 15 Feb 2023
Topic Review
GPR21 Inhibition
GPR21 is a constitutively active, orphan, Gq-protein-coupled receptor, with in vivo studies suggesting its involvement in the insulin resistance development.
  • 1.0K
  • 11 Nov 2021
Topic Review
Prejunctional 5-HT Receptors/Mechanisms and Modulation of Neurovascular Transmission
5-Hydroxytryptamine (5-HT), or serotonin, plays a crucial role as a neuromodulator and/or neurotransmitter of several nervous system functions. Its actions are complex, and depend on multiple factors, including the type of effector or receptor activated. Briefly, 5-HT can activate: (i) metabotropic (G-protein-coupled) receptors to promote inhibition (5-HT1, 5-HT5) or activation (5-HT4, 5-HT6, 5-HT7) of adenylate cyclase, as well as activation (5-HT2) of phospholipase C; and (ii) ionotropic receptor (5-HT3), a ligand-gated Na+/K+ channel. Regarding blood pressure regulation (and beyond the intricacy of central 5-HT effects), this monoamine also exerts direct postjunctional (on vascular smooth muscle and endothelium) or indirect prejunctional (on autonomic and sensory perivascular nerves) effects. At the prejunctional level, 5-HT can facilitate or preclude the release of autonomic (e.g., noradrenaline and acetylcholine) or sensory (e.g., calcitonin gene-related peptide) neurotransmitters facilitating hypertensive or hypotensive effects. Hence, we cannot formulate a specific impact of 5-HT on blood pressure level, since an increase or decrease in neurotransmitter release would be favoured, depending on the type of prejunctional receptor involved.
  • 1.0K
  • 14 Jul 2023
Topic Review
A Novel, Pan-PDE Inhibitor From the Group of 7,8-Disubstituted Purine-2,6-Dione Derivatives
Phosphodiesterases (PDEs) inhibitors are currently a widespread and extensively studied group of anti-inflammatory and anti-fibrotic compounds which may find use in the treatment of numerous lung diseases, including asthma and chronic obstructive pulmonary disease. Several PDE inhibitors are currently in clinical development, and some of them, e.g. roflumilast, are already recommended for clinical use. Due to numerous reports indicating that elevated intracellular adenosine 3’,5’-cyclic monophosphate (cAMP) levels may contribute to alleviation of inflammation and airway fibrosis, new and effective PDE inhibitors are constantly being sought. Recently, a group of 7,8-disubstituted purine-2,6-dione derivatives, representing novel and prominent pan-PDE inhibitors has been synthesized. Some of them were reported to modulate transient receptor potential ankyrin 1 (TRPA1) ion channels as well. Compound 145 (4-(8-butoxy-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(5-(tert-butyl)-2-hydroxyphenyl)butanamide) – a pan-PDE inhibitor and a weak TRPA1 modulator inhibited fibroblast to myofibroblasts transition (FMT) as well as MRC-5 human lung fibroblasts proliferation, migration, and contraction. The effect of this compound appeared to depend mainly on its strong PDE inhibitory properties, and not on its effects on TRPA1 modulation. The strong anti-remodelling effects of 145 required activation of the cAMP/protein kinase A/CREB pathway leading to inhibition of transforming growth factor type β1 (TGF-β1) and Smad-dependent signalling in MRC-5 cells.
  • 1.0K
  • 09 Sep 2021
Topic Review
Antimicrobial Peptides-Silver Nanoparticles for Methicillin-Resistance Staphylococcus aureus
Antibiotics are regarded as a miracle in the medical field as it prevents disease caused by pathogenic bacteria. Since the discovery of penicillin, antibiotics have become the foundation for modern medical discoveries. However, bacteria soon became resistant to antibiotics, which puts a burden on the healthcare system. Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most prominent antibiotic-resistant bacteria in the world since 1961. MRSA primarily developed resistance to beta-lactamases antibiotics and can be easily spread in the healthcare system. Thus, alternatives to combat MRSA are urgently required. Antimicrobial peptides (AMPs), an innate host immune agent and silver nanoparticles (AgNPs), are gaining interest as alternative treatments against MRSA. Both agents have broad-spectrum properties which are suitable candidates for controlling MRSA. Although both agents can exhibit antimicrobial effects independently, the combination of both can be synergistic and complementary to each other to exhibit stronger antimicrobial activity. The combination of AMPs and AgNPs also reduces their own weaknesses as their own, which can be developed as a potential agent to combat antibiotic resistance especially towards MRSA. 
  • 1.0K
  • 25 Jul 2022
Topic Review
DDS Based on Polysaccharides
Polysaccharides are polymeric carbohydrates composed of repeating monomeric units of monosaccharides that are covalently linked to each other through glucosidic linkage. Polysaccharides are biocompatible, biodegradable biopolymers, and the presence of various functional groups, such as hydroxyl, carboxyl, and amino groups, allow their easy chemical modification in order to increase their intrinsic properties (solubility, chemical stability, etc.). Due to these improved properties, polysaccharides are largely used as biomaterials in food, biomedical, pharmaceutical, cosmetic industry, and also as micellar drug-loaded systems. 
  • 1.0K
  • 12 Apr 2021
Topic Review
Glucosamine and Chondroitin for Osteoarthritis
Glucosamine is a water-soluble amino monosaccharide available in two forms (glucosamine sulphate and glucosamine hydrochloride), which is a normal constituent of glycosaminoglycans (GAGs) in cartilage matrix and in the synovial fluid and consequently present in high quantities in articular cartilage. It is a constituent of keratan sulphate. Chondroitin is a major component of the extracellular matrix of articular cartilage, which played an important role in creating considerable osmotic pressure. In this way, it could provide cartilage with resistance and elasticity to resist tensile stresses during loading conditions.
  • 1.0K
  • 31 Dec 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. 
  • 1.0K
  • 13 Apr 2022
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