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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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25 pages, 3870 KiB  
Opinion
Phage Cocktail Development for Bacteriophage Therapy: Toward Improving Spectrum of Activity Breadth and Depth
by Stephen T. Abedon, Katarzyna M. Danis-Wlodarczyk and Daniel J. Wozniak
Pharmaceuticals 2021, 14(10), 1019; https://doi.org/10.3390/ph14101019 - 03 Oct 2021
Cited by 68 | Viewed by 7302
Abstract
Phage therapy is the use of bacterial viruses as antibacterial agents. A primary consideration for commercial development of phages for phage therapy is the number of different bacterial strains that are successfully targeted, as this defines the breadth of a phage cocktail’s spectrum [...] Read more.
Phage therapy is the use of bacterial viruses as antibacterial agents. A primary consideration for commercial development of phages for phage therapy is the number of different bacterial strains that are successfully targeted, as this defines the breadth of a phage cocktail’s spectrum of activity. Alternatively, phage cocktails may be used to reduce the potential for bacteria to evolve phage resistance. This, as we consider here, is in part a function of a cocktail’s ‘depth’ of activity. Improved cocktail depth is achieved through inclusion of at least two phages able to infect a single bacterial strain, especially two phages against which bacterial mutation to cross resistance is relatively rare. Here, we consider the breadth of activity of phage cocktails while taking both depth of activity and bacterial mutation to cross resistance into account. This is done by building on familiar algorithms normally used for determination solely of phage cocktail breadth of activity. We show in particular how phage cocktails for phage therapy may be rationally designed toward enhancing the number of bacteria impacted while also reducing the potential for a subset of those bacteria to evolve phage resistance, all as based on previously determined phage properties. Full article
(This article belongs to the Special Issue Phage Therapy and Phage-Mediated Biological Control 2021)
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24 pages, 1135 KiB  
Article
Side Effects of mRNA-Based COVID-19 Vaccine: Nationwide Phase IV Study among Healthcare Workers in Slovakia
by Abanoub Riad, Barbora Hocková, Lucia Kantorová, Rastislav Slávik, Lucia Spurná, Adam Stebel, Michal Havriľak and Miloslav Klugar
Pharmaceuticals 2021, 14(9), 873; https://doi.org/10.3390/ph14090873 - 29 Aug 2021
Cited by 71 | Viewed by 12414
Abstract
mRNA-based COVID-19 vaccines such as BNT162b2 have recently been a target of anti-vaccination campaigns due to their novelty in the healthcare industry; nevertheless, these vaccines have exhibited excellent results in terms of efficacy and safety. As a consequence, they acquired the first approvals [...] Read more.
mRNA-based COVID-19 vaccines such as BNT162b2 have recently been a target of anti-vaccination campaigns due to their novelty in the healthcare industry; nevertheless, these vaccines have exhibited excellent results in terms of efficacy and safety. As a consequence, they acquired the first approvals from drug regulators and were deployed at a large scale among priority groups, including healthcare workers. This phase IV study was designed as a nationwide cross-sectional survey to evaluate the post-vaccination side effects among healthcare workers in Slovakia. The study used a validated self-administered questionnaire that inquired about participants’ demographic information, medical anamneses, COVID-19-related anamnesis, and local, systemic, oral, and skin-related side effects following receiving the BNT162b2 vaccine. A total of 522 participants were included in this study, of whom 77% were females, 55.7% were aged between 31 and 54 years, and 41.6% were from Banska Bystrica. Most of the participants (91.6%) reported at least one side effect. Injection site pain (85.2%) was the most common local side effect, while fatigue (54.2%), headache (34.3%), muscle pain (28.4%), and chills (26.4%) were the most common systemic side effects. The reported side effects were of a mild nature (99.6%) that did not require medical attention and a short duration, as most of them (90.4%) were resolved within three days. Females and young adults were more likely to report post-vaccination side effects; such a finding is also consistent with what was previously reported by other phase IV studies worldwide. The role of chronic illnesses and medical treatments in post-vaccination side effect incidence and intensity requires further robust investigation among large population groups. Full article
(This article belongs to the Special Issue Current Trends in RNA Virus Vaccines)
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16 pages, 328 KiB  
Review
Lung Fibrosis after COVID-19: Treatment Prospects
by Evgeny Bazdyrev, Polina Rusina, Maria Panova, Fedor Novikov, Ivan Grishagin and Vladimir Nebolsin
Pharmaceuticals 2021, 14(8), 807; https://doi.org/10.3390/ph14080807 - 17 Aug 2021
Cited by 97 | Viewed by 18216
Abstract
At the end of 2019, a highly contagious infection began its ominous conquest of the world. It was soon discovered that the disease was caused by a novel coronavirus designated as SARS-CoV-2, and the disease was thus abbreviated to COVID-19 (COVID). The global [...] Read more.
At the end of 2019, a highly contagious infection began its ominous conquest of the world. It was soon discovered that the disease was caused by a novel coronavirus designated as SARS-CoV-2, and the disease was thus abbreviated to COVID-19 (COVID). The global medical community has directed its efforts not only to find effective therapies against the deadly pathogen but also to combat the concomitant complications. Two of the most common respiratory manifestations of COVID are a significant reduction in the diffusing capacity of the lungs (DLCO) and the associated pulmonary interstitial damage. One year after moderate COVID, the incidence rate of impaired DLCO and persistent lung damage still exceeds 30%, and one-third of the patients have severe DLCO impairment and fibrotic lung damage. The persistent respiratory complications may cause substantial population morbidity, long-term disability, and even death due to the lung fibrosis progression. The incidence of COVID-induced pulmonary fibrosis caused by COVID can be estimated based on a 15-year observational study of lung pathology after SARS. Most SARS patients with fibrotic lung damage recovered within the first year and then remained healthy; however, in 20% of the cases, significant fibrosis progression was found in 5–10 years. Based on these data, the incidence rate of post-COVID lung fibrosis can be estimated at 2–6% after moderate illness. What is worse, there are reasons to believe that fibrosis may become one of the major long-term complications of COVID, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. In this review, we analyze the latest data from ongoing clinical trials aimed at treating post-COVID lung fibrosis and analyze the rationale for the current drug candidates. We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis, the IN01 vaccine, glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID-associated pulmonary damage. Full article
(This article belongs to the Special Issue Lung Injury and Repair)
32 pages, 2038 KiB  
Review
Pharmaceutical Drugs and Natural Therapeutic Products for the Treatment of Type 2 Diabetes Mellitus
by Jana Blahova, Monika Martiniakova, Martina Babikova, Veronika Kovacova, Vladimira Mondockova and Radoslav Omelka
Pharmaceuticals 2021, 14(8), 806; https://doi.org/10.3390/ph14080806 - 17 Aug 2021
Cited by 97 | Viewed by 14656
Abstract
Type 2 diabetes mellitus (T2DM) is the most widespread form of diabetes, characterized by chronic hyperglycaemia, insulin resistance, and inefficient insulin secretion and action. Primary care in T2DM is pharmacological, using drugs of several groups that include insulin sensitisers (e.g., biguanides, thiazolidinediones), insulin [...] Read more.
Type 2 diabetes mellitus (T2DM) is the most widespread form of diabetes, characterized by chronic hyperglycaemia, insulin resistance, and inefficient insulin secretion and action. Primary care in T2DM is pharmacological, using drugs of several groups that include insulin sensitisers (e.g., biguanides, thiazolidinediones), insulin secretagogues (e.g., sulphonylureas, meglinides), alpha-glucosidase inhibitors, and the newest incretin-based therapies and sodium–glucose co-transporter 2 inhibitors. However, their long-term application can cause many harmful side effects, emphasising the importance of the using natural therapeutic products. Natural health substances including non-flavonoid polyphenols (e.g., resveratrol, curcumin, tannins, and lignans), flavonoids (e.g., anthocyanins, epigallocatechin gallate, quercetin, naringin, rutin, and kaempferol), plant fruits, vegetables and other products (e.g., garlic, green tea, blackcurrant, rowanberry, bilberry, strawberry, cornelian cherry, olive oil, sesame oil, and carrot) may be a safer alternative to primary pharmacological therapy. They are recommended as food supplements to prevent and/or ameliorate T2DM-related complications. In the advanced stage of T2DM, the combination therapy of synthetic agents and natural compounds with synergistic interactions makes the treatment more efficient. In this review, both pharmaceutical drugs and selected natural products, as well as combination therapies, are characterized. Mechanisms of their action and possible negative side effects are also provided. Full article
(This article belongs to the Special Issue Multitarget Drug Discovery and Pharmacology)
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15 pages, 3667 KiB  
Article
Human Hair Keratin Composite Scaffold: Characterisation and Biocompatibility Study on NIH 3T3 Fibroblast Cells
by Jamal Moideen Muthu Mohamed, Ali Alqahtani, Adel Al Fatease, Taha Alqahtani, Barkat Ali Khan, B. Ashmitha and R. Vijaya
Pharmaceuticals 2021, 14(8), 781; https://doi.org/10.3390/ph14080781 - 09 Aug 2021
Cited by 25 | Viewed by 4275
Abstract
The aim of this study was to transform human hair keratin waste into a scaffold for soft tissue engineering to heal wounds. The keratin was extracted using the Shindai method. Keratin and polyvinyl alcohol (PVA) was cross-linked with alginate dialdehyde and converted into [...] Read more.
The aim of this study was to transform human hair keratin waste into a scaffold for soft tissue engineering to heal wounds. The keratin was extracted using the Shindai method. Keratin and polyvinyl alcohol (PVA) was cross-linked with alginate dialdehyde and converted into a scaffold by the freeze-drying method using gentamycin sulphate (GS) as a model drug. The scaffold was subjected to Fourier transform infrared spectra (FTIR), swelling index, porosity, water absorption, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), drug release, and cell viability (MTT) analysis. The scaffold was tested for keratinocyte growth using the murine fibroblast cell line (NIH 3T3 cells). The outcome from the keratin had a molecular weight band between 52–38 kDa in SDS-PAGE (Sodium dodecylsulfate-Polyacrylamide gel electrophoresis). A porous scaffold was capable of water absorption (73.64 ± 14.29%), swelling ability (68.93 ± 1.33%), and the release of GS shown as 97.45 ± 4.57 and 93.86 ± 5.22 of 1:4 and 1:3 scaffolds at 16 h. The physicochemical evaluation revealed that the prepared scaffold exhibits the proper structural integrity: partially crystalline with a strong thermal property. The scaffold demonstrated better cell viability against the murine fibroblast cell line (NIH 3T3 cells). In conclusion, we found that the prepared composite scaffold (1:4) can be used for wound healing applications. Full article
(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)
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40 pages, 8823 KiB  
Review
G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions
by Tiago Santos, Gilmar F. Salgado, Eurico J. Cabrita and Carla Cruz
Pharmaceuticals 2021, 14(8), 769; https://doi.org/10.3390/ph14080769 - 05 Aug 2021
Cited by 52 | Viewed by 8864
Abstract
Progress in the design of G-quadruplex (G4) binding ligands relies on the availability of approaches that assess the binding mode and nature of the interactions between G4 forming sequences and their putative ligands. The experimental approaches used to characterize G4/ligand interactions can be [...] Read more.
Progress in the design of G-quadruplex (G4) binding ligands relies on the availability of approaches that assess the binding mode and nature of the interactions between G4 forming sequences and their putative ligands. The experimental approaches used to characterize G4/ligand interactions can be categorized into structure-based methods (circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography), affinity and apparent affinity-based methods (surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS)), and high-throughput methods (fluorescence resonance energy transfer (FRET)-melting, G4-fluorescent intercalator displacement assay (G4-FID), affinity chromatography and microarrays. Each method has unique advantages and drawbacks, which makes it essential to select the ideal strategies for the biological question being addressed. The structural- and affinity and apparent affinity-based methods are in several cases complex and/or time-consuming and can be combined with fast and cheap high-throughput approaches to improve the design and development of new potential G4 ligands. In recent years, the joint use of these techniques permitted the discovery of a huge number of G4 ligands investigated for diagnostic and therapeutic purposes. Overall, this review article highlights in detail the most commonly used approaches to characterize the G4/ligand interactions, as well as the applications and types of information that can be obtained from the use of each technique. Full article
(This article belongs to the Special Issue Quadruplex Nucleic Acid Ligands in Drug Discovery)
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13 pages, 476 KiB  
Review
Immunotherapy Treatment for Triple Negative Breast Cancer
by Elizabeth R. Berger, Tristen Park, Angeleke Saridakis, Mehra Golshan, Rachel A. Greenup and Nita Ahuja
Pharmaceuticals 2021, 14(8), 763; https://doi.org/10.3390/ph14080763 - 04 Aug 2021
Cited by 31 | Viewed by 6463
Abstract
Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes of breast cancer and has dismal prognosis. Local recurrence rate after standard therapy in the early breast cancer setting can be upwards to 72% in 5 years, and in the metastatic setting, [...] Read more.
Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes of breast cancer and has dismal prognosis. Local recurrence rate after standard therapy in the early breast cancer setting can be upwards to 72% in 5 years, and in the metastatic setting, the 5-year overall survival is 12%. Due to the lack of receptor expression, there has been a paucity of targeted therapeutics available, with chemotherapy being the primary option for systemic treatment in both the neoadjuvant and metastatic setting. More recently, immunotherapy has revolutionized the landscape of cancer treatment, particularly immune checkpoint inhibitor (ICI) therapy, with FDA approval in over 20 types of cancer since 2011. Compared to other cancer types, breast cancer has been traditionally thought of as being immunologically cold; however, TNBC has demonstrated the most promise with immunotherapy use, a timely discovery due to its lack of targeted therapy options. In this review, we summarize the trials using checkpoint therapy in early and metastatic TNBC, as well as the development of biomarkers and the importance of immune related adverse events (IRAEs), in this disease process. Full article
(This article belongs to the Special Issue Potential Molecular Targets and Therapeutics in Triple-Negative Breast Cancer)
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39 pages, 2731 KiB  
Review
Pulmonary Delivery of Anticancer Drugs via Lipid-Based Nanocarriers for the Treatment of Lung Cancer: An Update
by Ibrahim M. Abdulbaqi, Reem Abou Assi, Anan Yaghmur, Yusrida Darwis, Noratiqah Mohtar, Thaigarajan Parumasivam, Fadi G. Saqallah and Habibah A. Wahab
Pharmaceuticals 2021, 14(8), 725; https://doi.org/10.3390/ph14080725 - 27 Jul 2021
Cited by 26 | Viewed by 6319
Abstract
Lung cancer (LC) is the leading cause of cancer-related deaths, responsible for approximately 18.4% of all cancer mortalities in both sexes combined. The use of systemic therapeutics remains one of the primary treatments for LC. However, the therapeutic efficacy of these agents is [...] Read more.
Lung cancer (LC) is the leading cause of cancer-related deaths, responsible for approximately 18.4% of all cancer mortalities in both sexes combined. The use of systemic therapeutics remains one of the primary treatments for LC. However, the therapeutic efficacy of these agents is limited due to their associated severe adverse effects, systemic toxicity and poor selectivity. In contrast, pulmonary delivery of anticancer drugs can provide many advantages over conventional routes. The inhalation route allows the direct delivery of chemotherapeutic agents to the target LC cells with high local concertation that may enhance the antitumor activity and lead to lower dosing and fewer systemic toxicities. Nevertheless, this route faces by many physiological barriers and technological challenges that may significantly affect the lung deposition, retention, and efficacy of anticancer drugs. The use of lipid-based nanocarriers could potentially overcome these problems owing to their unique characteristics, such as the ability to entrap drugs with various physicochemical properties, and their enhanced permeability and retention (EPR) effect for passive targeting. Besides, they can be functionalized with different targeting moieties for active targeting. This article highlights the physiological, physicochemical, and technological considerations for efficient inhalable anticancer delivery using lipid-based nanocarriers and their cutting-edge role in LC treatment. Full article
(This article belongs to the Special Issue Current Insights on Lipid-Based Nanosystems)
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30 pages, 5569 KiB  
Review
Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms
by Justyna Kowalska, Jakub Rok, Zuzanna Rzepka and Dorota Wrześniok
Pharmaceuticals 2021, 14(8), 723; https://doi.org/10.3390/ph14080723 - 26 Jul 2021
Cited by 29 | Viewed by 9424
Abstract
Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and [...] Read more.
Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells. Full article
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12 pages, 3410 KiB  
Review
[68Ga]Ga-PSMA-11: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging of Prostate Cancer
by Ute Hennrich and Matthias Eder
Pharmaceuticals 2021, 14(8), 713; https://doi.org/10.3390/ph14080713 - 23 Jul 2021
Cited by 56 | Viewed by 7336
Abstract
For the positron emission tomography (PET) imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. Almost 10 years after its discovery, [68Ga]Ga-PSMA-11 has been approved in the United States by the Food and [...] Read more.
For the positron emission tomography (PET) imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. Almost 10 years after its discovery, [68Ga]Ga-PSMA-11 has been approved in the United States by the Food and Drug Administration (FDA) as the first 68Ga-radiopharmaceutical for the PET imaging of PSMA-positive prostate cancer in 2020. This radiopharmaceutical combines the peptidomimetic Glu-NH-CO-NH-Lys(Ahx)-HBED-CC with the radionuclide 68Ga, enabling specific imaging of tumor cells expressing PSMA. Such a targeting approach may also be used for therapy planning as well as potentially for the evaluation of treatment response. Full article
(This article belongs to the Special Issue Targets, Tracers and Translation, Part 2 - New Horizons in Radiopharmaceutical Development)
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34 pages, 2870 KiB  
Review
Dietary Effects of Anthocyanins in Human Health: A Comprehensive Review
by Ana C. Gonçalves, Ana R. Nunes, Amílcar Falcão, Gilberto Alves and Luís R. Silva
Pharmaceuticals 2021, 14(7), 690; https://doi.org/10.3390/ph14070690 - 18 Jul 2021
Cited by 99 | Viewed by 10953
Abstract
In recent years, the consumption of natural-based foods, including beans, fruits, legumes, nuts, oils, vegetables, spices, and whole grains, has been encouraged. This fact is essentially due to their content in bioactive phytochemicals, with the phenolic compounds standing out. Among them, anthocyanins have [...] Read more.
In recent years, the consumption of natural-based foods, including beans, fruits, legumes, nuts, oils, vegetables, spices, and whole grains, has been encouraged. This fact is essentially due to their content in bioactive phytochemicals, with the phenolic compounds standing out. Among them, anthocyanins have been a target of many studies due to the presence of catechol, pyrogallol, and methoxy groups in their chemical structure, which confer notable scavenging, anti-apoptotic, and anti-inflammatory activities, being already recommended as supplementation to mitigate or even attenuate certain disorders, such as diabetes, cancer, and cardiovascular and neurological pathologies. The most well-known anthocyanins are cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside. They are widespread in nature, being present in considerable amounts in red fruits and red vegetables. Overall, the present review intends to discuss the most recent findings on the potential health benefits from the daily intake of anthocyanin-rich foods, as well as their possible pharmacological mechanisms of action. However, before that, some emphasis regarding their chemical structure, dietary sources, and bioavailability was done. Full article
(This article belongs to the Special Issue Plant and Marine-Derived Natural Product Research in Drug Discovery: Strengths and Perspective)
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19 pages, 1609 KiB  
Review
The Many Applications of Engineered Bacteriophages—An Overview
by Bryan Gibb, Paul Hyman and Christine L. Schneider
Pharmaceuticals 2021, 14(7), 634; https://doi.org/10.3390/ph14070634 - 30 Jun 2021
Cited by 35 | Viewed by 6439
Abstract
Since their independent discovery by Frederick Twort in 1915 and Felix d’Herelle in 1917, bacteriophages have captured the attention of scientists for more than a century. They are the most abundant organisms on the planet, often outnumbering their bacterial hosts by tenfold in [...] Read more.
Since their independent discovery by Frederick Twort in 1915 and Felix d’Herelle in 1917, bacteriophages have captured the attention of scientists for more than a century. They are the most abundant organisms on the planet, often outnumbering their bacterial hosts by tenfold in a given environment, and they constitute a vast reservoir of unexplored genetic information. The increased prevalence of antibiotic resistant pathogens has renewed interest in the use of naturally obtained phages to combat bacterial infections, aka phage therapy. The development of tools to modify phages, genetically or chemically, combined with their structural flexibility, cargo capacity, ease of propagation, and overall safety in humans has opened the door to a myriad of applications. This review article will introduce readers to many of the varied and ingenious ways in which researchers are modifying phages to move them well beyond their innate ability to target and kill bacteria. Full article
(This article belongs to the Special Issue Bacteriophages as Therapeutic Delivery Vehicles)
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50 pages, 10628 KiB  
Review
Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma
by Julie Bolcaen, Shankari Nair, Cathryn H. S. Driver, Tebatso M. G. Boshomane, Thomas Ebenhan and Charlot Vandevoorde
Pharmaceuticals 2021, 14(7), 626; https://doi.org/10.3390/ph14070626 - 29 Jun 2021
Cited by 12 | Viewed by 5305
Abstract
Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact [...] Read more.
Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals. Full article
(This article belongs to the Special Issue Targets, Tracers and Translation, Part 2 - New Horizons in Radiopharmaceutical Development)
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12 pages, 1307 KiB  
Article
Serum Extracellular Vesicle-Derived circHIPK3 and circSMARCA5 Are Two Novel Diagnostic Biomarkers for Glioblastoma Multiforme
by Michele Stella, Luca Falzone, Angela Caponnetto, Giuseppe Gattuso, Cristina Barbagallo, Rosalia Battaglia, Federica Mirabella, Giuseppe Broggi, Roberto Altieri, Francesco Certo, Rosario Caltabiano, Giuseppe Maria Vincenzo Barbagallo, Paolo Musumeci, Marco Ragusa, Cinzia Di Pietro, Massimo Libra, Michele Purrello and Davide Barbagallo
Pharmaceuticals 2021, 14(7), 618; https://doi.org/10.3390/ph14070618 - 27 Jun 2021
Cited by 65 | Viewed by 4363
Abstract
Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving the prognosis of this currently incurable disease. We suggest the use of serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) [...] Read more.
Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving the prognosis of this currently incurable disease. We suggest the use of serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) as highly stable minimally invasive diagnostic biomarkers for GBM diagnosis. EVs were isolated by size exclusion chromatography from sera of 23 GBM and 5 grade 3 glioma (GIII) patients, and 10 unaffected controls (UC). The expression of two candidate circRNAs (circSMARCA5 and circHIPK3) was assayed by droplet digital PCR. CircSMARCA5 and circHIPK3 were significantly less abundant in sEVs from GBM patients with respect to UC (fold-change (FC) of −2.15 and −1.92, respectively) and GIII (FC of −1.75 and −1.4, respectively). Receiver operating characteristic curve (ROC) analysis, based on the expression of sEV-derived circSMARCA5 and circHIPK3, allowed us to distinguish GBM from UC (area under the curve (AUC) 0.823 (0.667–0.979) and 0.855 (0.704 to 1.000), with a 95% confidence interval (CI), respectively). Multivariable ROC analysis, performed by combining the expression of sEV-derived circSMARCA5 and circHIPK3 with preoperative neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR) and lymphocyte to monocyte (LMR) ratios, three known diagnostic and prognostic GBM markers, allowed an improvement in the GBM diagnostic accuracy (AUC 0.901 (0.7912 to 1.000), 95% CI). Our data suggest sEV-derived circSMARCA5 and circHIPK3 as good diagnostic biomarkers for GBM, especially when associated with preoperative NLR, PLR and LMR. Full article
(This article belongs to the Special Issue Exosomes as a Tool for Disease Progression Monitoring in Humans and Animals)
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19 pages, 462 KiB  
Review
Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes
by Iris Bischoff-Kont and Robert Fürst
Pharmaceuticals 2021, 14(6), 571; https://doi.org/10.3390/ph14060571 - 15 Jun 2021
Cited by 66 | Viewed by 8402
Abstract
Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora [...] Read more.
Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora of pre-clinical studies demonstrated anti-cancer, anti-oxidative, or anti-inflammatory actions. 6-Shogaol is formed from 6-gingerol by dehydration and represents one of the main bioactive principles in dried ginger rhizomes. 6-Shogaol is characterized by a Michael acceptor moiety being reactive with nucleophiles. This review intends to compile important findings on the actions of 6-shogaol as an anti-inflammatory compound: in vivo, 6-shogaol inhibited leukocyte infiltration into inflamed tissue accompanied with reduction of edema swelling. In vitro and in vivo, 6-shogaol reduced inflammatory mediator systems such as COX-2 or iNOS, affected NFκB and MAPK signaling, and increased levels of cytoprotective HO-1. Interestingly, certain in vitro studies provided deeper mechanistic insights demonstrating the involvement of PPAR-γ, JNK/Nrf2, p38/HO-1, and NFκB in the anti-inflammatory actions of the compound. Although these studies provide promising evidence that 6-shogaol can be classified as an anti-inflammatory substance, the exact mechanism of action remains to be elucidated. Moreover, conclusive clinical data for anti-inflammatory actions of 6-shogaol are largely lacking. Full article
(This article belongs to the Special Issue Promising Anti-inflammatory Medicinal Plants—An Assessment of Bioavailability, Pharmacokinetics, Clinical Efficacy and Overview of New Methodological Approaches)
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46 pages, 758 KiB  
Review
Designer Benzodiazepines: A Review of Toxicology and Public Health Risks
by Pietro Brunetti, Raffaele Giorgetti, Adriano Tagliabracci, Marilyn A. Huestis and Francesco Paolo Busardò
Pharmaceuticals 2021, 14(6), 560; https://doi.org/10.3390/ph14060560 - 11 Jun 2021
Cited by 34 | Viewed by 12744
Abstract
The rising use of designer benzodiazepines (DBZD) is a cat-and-mouse game between organized crime and law enforcement. Non-prohibited benzodiazepines are introduced onto the global drug market and scheduled as rapidly as possible by international authorities. In response, DBZD are continuously modified to avoid [...] Read more.
The rising use of designer benzodiazepines (DBZD) is a cat-and-mouse game between organized crime and law enforcement. Non-prohibited benzodiazepines are introduced onto the global drug market and scheduled as rapidly as possible by international authorities. In response, DBZD are continuously modified to avoid legal sanctions and drug seizures and generally to increase the abuse potential of the DBZD. This results in an unpredictable fluctuation between the appearance and disappearance of DBZD in the illicit market. Thirty-one DBZD were considered for review after consulting the international early warning database, but only 3-hydroxyphenazepam, adinazolam, clonazolam, etizolam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, phenazepam and pyrazolam had sufficient data to contribute to this scoping review. A total of 49 reports describing 1 drug offense, 2 self-administration studies, 3 outpatient department admissions, 44 emergency department (ED) admissions, 63 driving under the influence of drugs (DUID) and 141 deaths reported between 2008 and 2021 are included in this study. Etizolam, flualprazolam flubromazolam and phenazepam were implicated in the majority of adverse-events, drug offenses and deaths. However, due to a general lack of knowledge of DBZD pharmacokinetics and toxicity, and due to a lack of validated analytical methods, total cases are much likely higher. Between 2019 and April 2020, DBZD were identified in 48% and 83% of postmortem and DUID cases reported to the UNODC, respectively, with flualprazolam, flubromazolam and etizolam as the most frequently detected substances. DBZD toxicology, public health risks and adverse events are reported. Full article
(This article belongs to the Special Issue Clinical and Forensic Toxicology: The Latest Updates)
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28 pages, 651 KiB  
Review
Clinical Management of COVID-19: A Review of Pharmacological Treatment Options
by Ashli M. Heustess, Melissa A. Allard, Dorothea K. Thompson and Pius S. Fasinu
Pharmaceuticals 2021, 14(6), 520; https://doi.org/10.3390/ph14060520 - 28 May 2021
Cited by 22 | Viewed by 7466
Abstract
Since the outbreak and subsequent declaration of COVID-19 as a global pandemic in March 2020, concerted efforts have been applied by the scientific community to curtail the spread of the disease and find a cure. While vaccines constitute a vital part of the [...] Read more.
Since the outbreak and subsequent declaration of COVID-19 as a global pandemic in March 2020, concerted efforts have been applied by the scientific community to curtail the spread of the disease and find a cure. While vaccines constitute a vital part of the public health strategy to reduce the burden of COVID-19, the management of this disease will continue to rely heavily on pharmacotherapy. This study aims to provide an updated review of pharmacological agents that have been developed and/or repurposed for the treatment of COVID-19. To this end, a comprehensive literature search was conducted using the PubMed, Google Scholar, and LitCovid databases. Relevant clinical studies on drugs used in the management of COVID-19 were identified and evaluated in terms of evidence of efficacy and safety. To date, the FDA has approved three therapies for the treatment of COVID-19 Emergency Use Authorization: convalescent plasma, remdesivir, and casirivimab/imdevimab (REGN-COV2). Drugs such as lopinavir/ritonavir, umifenovir, favipiravir, anakinra, chloroquine, hydroxychloroquine, tocilizumab, interferons, tissue plasminogen activator, intravenous immunoglobulins, and nafamosat have been used off-label with mixed therapeutic results. Adjunctive administration of corticosteroids is also very common. The clinical experience with these approved and repurposed drugs is limited, and data on efficacy for the new indication are not strong. Overall, the response of the global scientific community to the COVID-19 pandemic has been impressive, as evident from the volume of scientific literature elucidating the molecular biology and pathophysiology of SARS-CoV-2 and the approval of three new drugs for clinical management. Reviewed studies have shown mixed data on efficacy and safety of the currently utilized drugs. The lack of standard treatment for COVID-19 has made it difficult to interpret results from most of the published studies due to the risk of attribution error. The long-term effects of drugs can only be assessed after several years of clinical experience; therefore, the efficacy and safety of current COVID-19 therapeutics should continue to be rigorously monitored as part of post-marketing studies. Full article
(This article belongs to the Special Issue COVID-19 in Pharmaceuticals)
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29 pages, 1680 KiB  
Review
Current Prospects for Treatment of Solid Tumors via Photodynamic, Photothermal, or Ionizing Radiation Therapies Combined with Immune Checkpoint Inhibition (A Review)
by Sanjay Anand, Timothy A. Chan, Tayyaba Hasan and Edward V. Maytin
Pharmaceuticals 2021, 14(5), 447; https://doi.org/10.3390/ph14050447 - 10 May 2021
Cited by 32 | Viewed by 3666
Abstract
Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy [...] Read more.
Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy to destroy cancer tissue. Ionizing radiation therapy (RT) and photothermal therapy (PTT) are two other treatment modalities that employ photons (with wavelengths either shorter or longer than PDT, respectively) and also cause tissue damage and immunomodulation. Research on the three modalities has occurred in different “silos”, with minimal interaction between the three topics. This is happening at a time when immune checkpoint inhibition (ICI), another focus of intense research and clinical development, has opened exciting possibilities for combining PDT, PTT, or RT with ICI to achieve improved therapeutic benefits. In this review, we surveyed the literature for studies that describe changes in anti-tumor immunity following the administration of PDT, PTT, and RT, including efforts to combine each modality with ICI. This information, collected all in one place, may make it easier to recognize similarities and differences and help to identify new mechanistic hypotheses toward the goal of achieving optimized combinations and tumor cures. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2021)
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28 pages, 693 KiB  
Review
COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials
by Zhi-Peng Yan, Ming Yang and Ching-Lung Lai
Pharmaceuticals 2021, 14(5), 406; https://doi.org/10.3390/ph14050406 - 25 Apr 2021
Cited by 100 | Viewed by 17509
Abstract
Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The [...] Read more.
Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations. Full article
(This article belongs to the Special Issue Current Trends in RNA Virus Vaccines)
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25 pages, 4268 KiB  
Article
A Novel Combination Therapy Using Rosuvastatin and Lactobacillus Combats Dextran Sodium Sulfate-Induced Colitis in High-Fat Diet-Fed Rats by Targeting the TXNIP/NLRP3 Interaction and Influencing Gut Microbiome Composition
by Sameh Saber, Eslam E. Abd El-Fattah, Galal Yahya, Naglaa A. Gobba, Abdalkareem Omar Maghmomeh, Ahmed E. Khodir, Ahmed A. E. Mourad, Ahmed S. Saad, Hager G. Mohammed, Nehal A. Nouh, Ahmed Shata, Noha A. Amin, Magdy Abou El-Rous, Samuel Girgis, Eman El-Ahwany, Eman M. Khalaf, Attalla F. El-Kott and Ahmed M. El-Baz
Pharmaceuticals 2021, 14(4), 341; https://doi.org/10.3390/ph14040341 - 08 Apr 2021
Cited by 39 | Viewed by 4862
Abstract
Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and Lactobacillus and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet [...] Read more.
Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and Lactobacillus and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet (HFD)-fed rats. Our results demonstrate the aggravation of intestinal inflammation as a consequence of an HFD following DSS administration. An association between dyslipidemia, LDL oxidation, CD36 expression, ROS generation, thioredoxin-interacting protein (TXNIP) upregulation, and NLRP3 inflammasome activation was demonstrated by DSS exposure in HFD-fed rats. We demonstrated that rosuvastatin/Lactobacillus significantly suppressed the DSS/HFD-induced increase in colon weight/length ratio, DAI, MDI, and myeloperoxidase, as well as corrected dysbiosis and improved histological characteristics. Additionally, caspase-1 activity and IL-1β-driven pyroptotic activity was significantly reduced. Rosuvastatin/Lactobacillus showed prominent anti-inflammatory effects as revealed by the IL-10/IL-12 ratio and the levels of TNF-α and IL-6. These latter effects may be attributed to the inhibition of phosphorylation-induced activation of NF-κB and a concomitant reduction in the expression of NLRP3, pro-IL-1β, and pro-IL-18. Furthermore, rosuvastatin/Lactobacillus reduced Ox-LDL-induced TXNIP and attenuated the inflammatory response by inhibiting NLRP3 inflammasome assembly. To conclude, rosuvastatin/Lactobacillus offers a safe and effective strategy for the management of ulcerative colitis. Full article
(This article belongs to the Special Issue Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets)
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21 pages, 1746 KiB  
Review
Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients
by Annalisa Noce, Maria Albanese, Giulia Marrone, Manuela Di Lauro, Anna Pietroboni Zaitseva, Daniela Palazzetti, Cristina Guerriero, Agostino Paolino, Giuseppa Pizzenti, Francesca Di Daniele, Annalisa Romani, Cartesio D’Agostini, Andrea Magrini, Nicola Biagio Mercuri and Nicola Di Daniele
Pharmaceuticals 2021, 14(4), 336; https://doi.org/10.3390/ph14040336 - 06 Apr 2021
Cited by 21 | Viewed by 8116
Abstract
The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, [...] Read more.
The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, in acute respiratory distress syndrome (ARDS). However, COVID-19 affects other organs and systems, including cardiovascular, urinary, gastrointestinal, and nervous systems. Currently, unique-drug therapy is not supported by international guidelines. In this context, it is important to resort to adjuvant therapies in combination with traditional pharmacological treatments. Among natural bioactive compounds, palmitoylethanolamide (PEA) seems to have potentially beneficial effects. In fact, the Food and Drug Administration (FDA) authorized an ongoing clinical trial with ultramicronized (um)-PEA as an add-on therapy in the treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. In support of this hypothesis, in vitro and in vivo studies have highlighted the immunomodulatory, anti-inflammatory, neuroprotective and pain-relieving effects of PEA, especially in its um form. The purpose of this review is to highlight the potential use of um-PEA as an adjuvant treatment in SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue COVID-19 in Pharmaceuticals)
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18 pages, 2669 KiB  
Article
Covalently Functionalized Carbon Nano-Onions Integrated Gelatin Methacryloyl Nanocomposite Hydrogel Containing γ-Cyclodextrin as Drug Carrier for High-Performance pH-Triggered Drug Release
by Narsimha Mamidi, Ramiro Manuel Velasco Delgadillo and Enrique V. Barrera
Pharmaceuticals 2021, 14(4), 291; https://doi.org/10.3390/ph14040291 - 25 Mar 2021
Cited by 55 | Viewed by 5395
Abstract
Herein, poly (n-(4-aminophenyl) methacrylamide)) carbon nano-onions (PAPMA-CNOs = f-CNOs) and γ-cyclodextrin/DOX-complex (CD) reinforced gelatin methacryloyl (GelMA)/f-CNOs/CD supramolecular hydrogel interfaces were fabricated using the photo-crosslinking technique. The physicochemical properties, morphology, biodegradation, and swelling properties of hydrogels were investigated. The composite hydrogels demonstrated [...] Read more.
Herein, poly (n-(4-aminophenyl) methacrylamide)) carbon nano-onions (PAPMA-CNOs = f-CNOs) and γ-cyclodextrin/DOX-complex (CD) reinforced gelatin methacryloyl (GelMA)/f-CNOs/CD supramolecular hydrogel interfaces were fabricated using the photo-crosslinking technique. The physicochemical properties, morphology, biodegradation, and swelling properties of hydrogels were investigated. The composite hydrogels demonstrated enriched drug release under the acidic conditions (pH 4.5 = 99%, and pH 6.0 = 82%) over 18 days. Owing to the f-CNOs inclusion, GelMA/f-CNOs/CD supramolecular hydrogels presented augmented tensile strength (σult = 356.1 ± 3.4 MPa), toughness (K = 51.5 ± 0.24 Jg−1), and Young’s modulus (E = 41.8 ± 1.4 GPa). The strengthening of GelMA/f-CNOs/CD hydrogel systems indicates its good dispersion and the degree of polymer enveloping of f-CNOs within GelMA matrixes. Furthermore, the obtained hydrogels showed improved cell viability with human fibroblast cells. Nevertheless, the primed supramolecular hydrogels would pave the way for the controlled delivery systems for future drug delivery. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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26 pages, 953 KiB  
Review
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences
by Marco Carli, Shivakumar Kolachalam, Biancamaria Longoni, Anna Pintaudi, Marco Baldini, Stefano Aringhieri, Irene Fasciani, Paolo Annibale, Roberto Maggio and Marco Scarselli
Pharmaceuticals 2021, 14(3), 238; https://doi.org/10.3390/ph14030238 - 08 Mar 2021
Cited by 84 | Viewed by 13598
Abstract
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life [...] Read more.
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well. Full article
(This article belongs to the Special Issue Molecular and Cellular Targets of Old and New Atypical Antipsychotics)
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18 pages, 10479 KiB  
Article
Repurposing of Some Natural Product Isolates as SARS-COV-2 Main Protease Inhibitors via In Vitro Cell Free and Cell-Based Antiviral Assessments and Molecular Modeling Approaches
by Hossam M. Abdallah, Ali M. El-Halawany, Alaa Sirwi, Amr M. El-Araby, Gamal A. Mohamed, Sabrin R. M. Ibrahim, Abdulrahman E. Koshak, Hani Z. Asfour, Zuhier A. Awan and Mahmoud A. Elfaky
Pharmaceuticals 2021, 14(3), 213; https://doi.org/10.3390/ph14030213 - 04 Mar 2021
Cited by 46 | Viewed by 4403
Abstract
The emergence of the SARS-CoV-2 pandemic has prompted scientists to search for an efficient antiviral medicine to overcome the rapid spread and the marked increase in the number of patients worldwide. In this regard natural products could be a potential source of substances [...] Read more.
The emergence of the SARS-CoV-2 pandemic has prompted scientists to search for an efficient antiviral medicine to overcome the rapid spread and the marked increase in the number of patients worldwide. In this regard natural products could be a potential source of substances active against coronavirus infections. A systematic computer-aided virtual screening approach was carried out using commercially available natural products found on the Zinc Database in addition to an in-house compound library to identify potential natural product inhibitors of SARS-CoV-2 main protease (MPRO). The top eighteen hits from the screening were selected for in vitro evaluation on the viral protease (SARS-CoV-2 MPRO). Five compounds (naringenin, 2,3′,4,5′,6-pentahydroxybenzophenone, apigenin-7-O-glucoside, sennoside B, and acetoside) displayed high activity against the viral protein. Acteoside showed similar activity to the positive control GC376. The most potent compounds were tested in vitro on SARS-CoV-2 Egyptian strain where only naringenin showed moderate anti-SARS-CoV-2 activity at non-cytotoxic micromolar concentrations in vitro with a significant selectivity index (CC50/IC50 = 178.748/28.347 = 6.3). Moreover; a common feature pharmacophore model was generated to explain the requirements for enzyme inhibition by this diverse group of active ligands. These results pave a path for future repurposing and development of natural products to aid in the battle against COVID-19. Full article
(This article belongs to the Special Issue Identification of Phytochemicals and Derivatives against Infectious Diseases)
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14 pages, 1726 KiB  
Review
2020 FDA TIDES (Peptides and Oligonucleotides) Harvest
by Othman Al Musaimi, Danah Al Shaer, Fernando Albericio and Beatriz G. de la Torre
Pharmaceuticals 2021, 14(2), 145; https://doi.org/10.3390/ph14020145 - 11 Feb 2021
Cited by 50 | Viewed by 5205
Abstract
2020 has been an extremely difficult and challenging year as a result of the coronavirus disease 2019 (COVID-19) pandemic and one in which most efforts have been channeled into tackling the global health crisis. The US Food and Drug Administration (FDA) has approved [...] Read more.
2020 has been an extremely difficult and challenging year as a result of the coronavirus disease 2019 (COVID-19) pandemic and one in which most efforts have been channeled into tackling the global health crisis. The US Food and Drug Administration (FDA) has approved 53 new drug entities, six of which fall in the peptides and oligonucleotides (TIDES) category. The number of authorizations for these kinds of drugs has been similar to that of previous years, thereby reflecting the consolidation of the TIDES market. Here, the TIDES approved in 2020 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects. Full article
(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)
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21 pages, 4303 KiB  
Article
Photophysical Properties of Protoporphyrin IX, Pyropheophorbide-a, and Photofrin® in Different Conditions
by Bauyrzhan Myrzakhmetov, Philippe Arnoux, Serge Mordon, Samir Acherar, Irina Tsoy and Céline Frochot
Pharmaceuticals 2021, 14(2), 138; https://doi.org/10.3390/ph14020138 - 09 Feb 2021
Cited by 43 | Viewed by 4592
Abstract
Photodynamic therapy (PDT) is an innovative treatment of malignant or diseased tissues. The effectiveness of PDT depends on light dosimetry, oxygen availability, and properties of the photosensitizer (PS). Depending on the medium, photophysical properties of the PS can change leading to increase or [...] Read more.
Photodynamic therapy (PDT) is an innovative treatment of malignant or diseased tissues. The effectiveness of PDT depends on light dosimetry, oxygen availability, and properties of the photosensitizer (PS). Depending on the medium, photophysical properties of the PS can change leading to increase or decrease in fluorescence emission and formation of reactive oxygen species (ROS) especially singlet oxygen (1O2). In this study, the influence of solvent polarity, viscosity, concentration, temperature, and pH medium on the photophysical properties of protoporphyrin IX, pyropheophorbide-a, and Photofrin® were investigated by UV-visible absorption, fluorescence emission, singlet oxygen emission, and time-resolved fluorescence spectroscopies. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2021)
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23 pages, 7117 KiB  
Review
Monofunctional Platinum(II) Anticancer Agents
by Suxing Jin, Yan Guo, Zijian Guo and Xiaoyong Wang
Pharmaceuticals 2021, 14(2), 133; https://doi.org/10.3390/ph14020133 - 07 Feb 2021
Cited by 36 | Viewed by 4792
Abstract
Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these [...] Read more.
Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these drugs. Among multifarious designs, monofunctional platinum(II) complexes with a general formula of [Pt(3A)Cl]+ (A: Ammonia or amine) stand out as a class of “non-traditional” anticancer agents hopeful to overcome the defects of current platinum drugs. This review aims to summarize the development of monofunctional platinum(II) complexes in recent years. They are classified into four categories: fluorescent complexes, photoactive complexes, targeted complexes, and miscellaneous complexes. The intention behind the designs is either to visualize the cellular distribution, or to reduce the side effects, or to improve the tumor selectivity, or inhibit the cancer cells through non-DNA targets. The information provided by this review may inspire researchers to conceive more innovative complexes with potent efficacy to shake off the drawbacks of platinum anticancer drugs. Full article
(This article belongs to the Special Issue Applications of Medicinal Bioinorganic Chemistry)
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33 pages, 1094 KiB  
Review
The Current and Potential Therapeutic Use of Metformin—The Good Old Drug
by Józef Drzewoski and Markolf Hanefeld
Pharmaceuticals 2021, 14(2), 122; https://doi.org/10.3390/ph14020122 - 05 Feb 2021
Cited by 55 | Viewed by 12792
Abstract
Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical [...] Read more.
Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases. Full article
(This article belongs to the Special Issue Metformin: Mechanism and Application 2022)
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21 pages, 719 KiB  
Review
Informing Patients about Biosimilar Medicines: The Role of European Patient Associations
by Yannick Vandenplas, Steven Simoens, Philippe Van Wilder, Arnold G. Vulto and Isabelle Huys
Pharmaceuticals 2021, 14(2), 117; https://doi.org/10.3390/ph14020117 - 04 Feb 2021
Cited by 29 | Viewed by 4854
Abstract
Biosimilar medicines support the sustainability of national healthcare systems, by reducing costs of biological therapies through increased competition. However, their adoption into clinical practice largely depends on the acceptance of healthcare providers and patients. Patients are different from health care professionals (HCPs), who [...] Read more.
Biosimilar medicines support the sustainability of national healthcare systems, by reducing costs of biological therapies through increased competition. However, their adoption into clinical practice largely depends on the acceptance of healthcare providers and patients. Patients are different from health care professionals (HCPs), who are informing themselves professionally. For patients, the biosimilar debate only becomes actual when they are confronted with disease and drug choices. This paper provides a literature review on how patients are and should be informed about biosimilars, searching in scientific databases (i.e., Medline, Embase). Several large surveys have shown a lack of knowledge and trust in biosimilars among European patients in recent years. This review identified five main strategies to inform patients about biosimilars: (1) provide understandable information, (2) in a positive and transparent way, (3) tailored to the individual’s needs, (4) with one voice, and (5) supported by audiovisual material. Moreover, the importance of a multistakeholder approach was underlined by describing the role of each stakeholder. Patients are a large and diffuse target group to be reached by educational programs. Therefore, patient associations have become increasingly important in correctly informing patients about biosimilar medicines. This has led to widespread biosimilar information for patients among European patient associations. Therefore, a web-based screening of European Patients’ Forum (EPF) and International Alliance of Patients’ Organizations (IAPO) member organizations on publicly available information about biosimilars was performed. We found that the level of detail, correctness, and the tone of the provided information varied. In conclusion, it is paramount to set up a close collaboration between all stakeholders to communicate, develop, and disseminate factual information about biosimilars for patients. Full article
(This article belongs to the Special Issue Biosimilars in Europe)
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12 pages, 1330 KiB  
Review
Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease
by Caitlin V. M. L. Jie, Valerie Treyer, Roger Schibli and Linjing Mu
Pharmaceuticals 2021, 14(2), 110; https://doi.org/10.3390/ph14020110 - 30 Jan 2021
Cited by 47 | Viewed by 8492
Abstract
Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one [...] Read more.
Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic. Full article
(This article belongs to the Special Issue Targets, Tracers and Translation, Part 2 - New Horizons in Radiopharmaceutical Development)
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23 pages, 4177 KiB  
Review
Repurposing Clinical Agents for Chemical Exchange Saturation Transfer Magnetic Resonance Imaging: Current Status and Future Perspectives
by Zelong Chen, Zheng Han and Guanshu Liu
Pharmaceuticals 2021, 14(1), 11; https://doi.org/10.3390/ph14010011 - 24 Dec 2020
Cited by 14 | Viewed by 3958
Abstract
Molecular imaging is becoming an indispensable tool to pursue precision medicine. However, quickly translating newly developed magnetic resonance imaging (MRI) agents into clinical use remains a formidable challenge. Recently, Chemical Exchange Saturation Transfer (CEST) MRI is emerging as an attractive approach with the [...] Read more.
Molecular imaging is becoming an indispensable tool to pursue precision medicine. However, quickly translating newly developed magnetic resonance imaging (MRI) agents into clinical use remains a formidable challenge. Recently, Chemical Exchange Saturation Transfer (CEST) MRI is emerging as an attractive approach with the capability of directly using low concentration, exchangeable protons-containing agents for generating quantitative MRI contrast. The ability to utilize diamagnetic compounds has been extensively exploited to detect many clinical compounds, such as FDA approved drugs, X-ray/CT contrast agents, nutrients, supplements, and biopolymers. The ability to directly off-label use clinical compounds permits CEST MRI to be rapidly translated to clinical settings. In this review, the current status of CEST MRI based on clinically available compounds will be briefly introduced. The advancements and limitations of these studies are reviewed in the context of their pre-clinical or clinical applications. Finally, future directions will be briefly discussed. Full article
(This article belongs to the Special Issue Next Generation of MRI Agents)
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