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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.
  • 708
  • 28 Oct 2020
Topic Review
Clozapine, Pharmacogenetic Biomarkers, Particularities COVID-19
Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed andWeb of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor then the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.
  • 705
  • 20 Nov 2020
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.
  • 705
  • 11 Nov 2021
Topic Review
Bazedoxifene Acetate
Bazedoxifene acetate, BZA, a third-generation selective estrogen receptor modulator (SERM), is an indole-based estrogen receptor ligand currently used to prevent and treat postmenopausal osteoporosis.
  • 704
  • 03 Nov 2021
Topic Review
Curcumin-Loaded Silica Nanoparticles
Curcumin has multiple properties that are used to cure different diseases such as cancer, infections, inflammatory, arthritic disease, etc. Despite having many effects, the inherent physicochemical properties—such as poor water solubility, chemical instability, low bioavailability, photodegradation, fast metabolism, and short half-life—of curcumin’s derivatives have limited its medical importance. Mesoporous silica nanoparticles (MSNs) are promising drug delivery systems for more effective and safer treatment of several diseases, such as infections, cancers, and osteoporosis. Achieving a high drug loading in MSNs is critical to the success of this type of treatment. Their notable inherent properties—such as adjustable size and porosity, high pore volume, large surface area, functionality of versatile surfaces, as well as biocompatibility—have prompted extraordinary research on MSNs as multi-purpose delivery platforms.
  • 704
  • 08 Sep 2022
Topic Review
Combination Therapy for Glioblastoma
Aggressive glioblastoma (GBM) has no known treatment as a primary brain tumor. Since the cancer is so heterogeneous, an immunosuppressive tumor microenvironment (TME) exists, and the blood–brain barrier (BBB) prevents chemotherapeutic chemicals from reaching the central nervous system (CNS), therapeutic success for GBM has been restricted. Drug delivery based on nanocarriers and nanotechnology has the potential to be a handy tool in the continuing effort to combat the challenges of treating GBM. Combination therapies may be enhanced by using nanotechnology-based delivery techniques. Nano-chemotherapy, nano-chemotherapy–radiation, nano-chemotherapy–phototherapy, and nano-chemotherapy–immunotherapy for GBM.
  • 704
  • 02 Nov 2022
Topic Review
Strategies for Improving Transdermal Administration
A transdermal delivery system is a painless method of drug administration through intact skin. Transdermal patches favor the controlled release of active ingredients through the skin into systemic circulation.Substances with analgesic effects can be administered on the skin in the form of topical patches made to produce local effects or transdermal patches that ensure the controlled and prolonged release of the active substance.
  • 703
  • 18 Apr 2023
Topic Review
Encapsulation of Interferon
Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been used in different presentations for several therapy applications. However, their administration has presented difficulties due to the molecules’ size, sensitivity to degradation, and rapid elimination from the bloodstream. An alternative to overcome these drawbacks is to formulate drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. 
  • 702
  • 09 Oct 2021
Topic Review
Anti-Leishmania Drug Delivery Systems
Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2-dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-L-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 μM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 μM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.
  • 702
  • 20 Oct 2020
Topic Review
Cardiac Fibrosis and Fibroblasts
Cardiac fibrosis is the excess deposition of extracellular matrix (ECM), such as collagen.
  • 701
  • 23 Jul 2021
Topic Review
Diabetic Micro-Complication Management—Diabetic Neuropathy
The progression of diabetes leads to macro and microvascular complications, including diabetic neuropathy, which is the most prevalent microvascular complication with diabetes. Clinical manifestations of diabetic neuropathy begin with the loss of distal sensory function, pain, and substantial morbidity.
  • 701
  • 11 Nov 2021
Topic Review
The Subcutaneous Route of Administration for Therapeutic Antibodies
Therapeutic antibodies (Abs) are used in the treatment of numerous diseases, including infection, cancer, and autoimmune disorders, in which they have already demonstrated their efficacy. The success of Abs is due to (I) a high level of specificity and affinity to their target antigen, (II) a favorable safety profile, and (III) a unique pharmacokinetic profile, supporting a longer half-life as compared to other drugs. While the majority of Abs are delivered through IV injection, evidence in the literature showed that beyond the reduction of invasiveness, a better efficacy could be achieved with a local delivery of Abs. Among those routes, one has been in full development these last few years, with already good clinical results and still promising developments: The Subcutaneous route.
  • 701
  • 13 Sep 2022
Topic Review
Binding of Cholesterol to GPCRs
G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30% of currently marketed drugs.
  • 700
  • 27 Mar 2021
Topic Review
Anticancer Secondary Metabolites of Astragalus Species
Some of the most effective anticancer compounds are still derived from plants since the chemical synthesis of chiral molecules is not economically efficient. Rapid discovery of lead compounds with pronounced biological activity is essential for the successful development of novel drug candidates. The genus Astragalus L. is the largest in the family Fabaceae (syn. Leguminosae), with more than 3500 species. Astragalus, excluding Astracantha (formerly Astragalus subgenus Tragacantha), has a world total of ca. 2500 species, of which ca. 500 are in the Americas. Many of the species have conservation status “vulnerable” or “critically endangered”.
  • 700
  • 09 Sep 2022
Topic Review
The Anti-Neuroinflammatory Role of Anthocyanins
Anthocyanins are a large subclass of flavonoids, widely distributed in fruits and vegetables in the human diet. Among flavonoids, anthocyanins have gained prominence mainly due to their high intake in humans and their well-recognized antioxidant and anti-inflammatory activities [10,12], among others, making them promising agents for the prevention and treatment of distinct pathological conditions, such as cardiometabolic diseases, cancer, vision impairment, and neurological diseases [11,13,14,15,16,17].
  • 699
  • 11 Jan 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). 
  • 699
  • 12 Apr 2021
Topic Review
Interplay between Drugs and Mycotoxins
Mycotoxin contamination is a global food safety issue leading to major public health concerns. Repeated exposure to multiple mycotoxins not only has repercussions on human health but could theoretically also lead to interactions with other xenobiotic substances—such as drugs—in the body by altering their pharmacokinetics and/or pharmacodynamics. The combined effects of chronic drug use and mycotoxin exposure need to be well understood in order to draw valid conclusions and, in due course, to develop guidelines.
  • 698
  • 21 Dec 2022
Topic Review
Multiple Functions of Melatonin in the Military Setting
Melatonin is a technique that is being increasingly employed to manage growing psycho-physical loads. In this context, melatonin, a pleotropic and regulatory molecule, has a potential preventive and therapeutic role in maintaining the operational efficiency of military personnel. In battlefield conditions in particular, the time to treatment after an injury is often a major issue since the injured may not have immediate access to medical care. Any drug that would help to stabilize a wounded individual, especially if it can be immediately administered (e.g., per os) and has a very high safety profile over a large range of doses (as melatonin does) would be an important asset to reduce morbidity and mortality.
  • 698
  • 06 Feb 2023
Topic Review
Nanodelivery Systems for Herbal/Phytoconstituents
Herbs and spices have been historically characterized as plant components utilized in the diet for their fragrant characteristics, but have no or minimal nutritional value. Herbs and spices, on the other hand, have been found as sources of different phytochemicals with strong antioxidant activity. As a result, phytoconstituents from herbs and spices can be formulated in various forms of nano-drug delivery systems.
  • 695
  • 29 Dec 2022
Topic Review
Anticancer Potential of Piper nigrum
Current anticancer therapy suffers from several limitations, including lack of selectivity and multidrug resistance. Natural products represent an excellent opportunity for the identification of new therapeutic options due to their safety, low toxicity, and general availability. Piper nigrum is one of the most popular species in the world, with growing fame as a source of bioactive molecules with pharmacological properties. Undeniable anticancer properties are reportetd for different Piper nigrum constituents, such as its main alkaloid piperine.
  • 694
  • 27 Feb 2021
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