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Future Pharmacol., Volume 1, Issue 1 (December 2021) – 7 articles

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24 pages, 2742 KiB  
Review
Recent Advances in Mupirocin Delivery Strategies for the Treatment of Bacterial Skin and Soft Tissue Infection
by Aishwarya Gangwar, Parveen Kumar, Ranjit Singh and Preeti Kush
Future Pharmacol. 2021, 1(1), 80-103; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010007 - 20 Dec 2021
Cited by 12 | Viewed by 9992
Abstract
Skin and soft tissue infections (SSTIs) have increased problematically in hospital and ambulatory settings due to the poor immunity of hosts and multidrug-resistant pathogens. Mupirocin (MUP), a global topical antibiotic, is used for the treatment of SSTIs caused by various pathogens due to [...] Read more.
Skin and soft tissue infections (SSTIs) have increased problematically in hospital and ambulatory settings due to the poor immunity of hosts and multidrug-resistant pathogens. Mupirocin (MUP), a global topical antibiotic, is used for the treatment of SSTIs caused by various pathogens due to its unique mechanism of action. However, the therapeutic efficiency of MUP is hampered due to the protein binding and drug resistance caused by frequent use. A combined report covering the various aspects of MUP, such as the synthesis of the novel formulation, loading of the drug, and application against various skin infections, is missing. This comprehensive review focuses on various novel drug delivery strategies such as composite biomaterials/scaffold, hydrogel dressings, liposomes, liposomal hydrogel, microparticles/microspheres, microsponges, nanocapsules, nanofibers, silicone-based adhesive patches, and topical sprays. The therapeutic effect of the MUP can be synergized by combining with other agents and using novel strategies. The objective is to enhance patient compliance, decrease the resistance, magnify the delivery of MUP, and overcome the limitations of conventional formulations. Moreover, the carriers/dressing materials are biocompatible, biodegradable, stimulate wound healing, protect the wound from external environmental contamination, adsorb the wound exudates, and are permeable to oxygen and moisture. This review will help researchers to explore further the treatment of various bacterial skin infections by using MUP-loaded novel formulations with better efficacy, utilizing the novel nanostructures or combinatorial methods. Full article
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20 pages, 5388 KiB  
Article
Virtual Screening of Adenylate Kinase 3 Inhibitors Employing Pharmacophoric Model, Molecular Docking, and Molecular Dynamics Simulations as Potential Therapeutic Target in Chronic Lymphocytic Leukemia
by Bárbara Lima Fonseca Barbosa, Tulio Resende Freitas, Michell de Oliveira Almeida, Sérgio Schusterschitz da Silva Araújo, Ana Clara Andrade, Geovana Gomes Dornelas, Julyana Gayva Fiorotto, Vinicius Gonçalves Maltarollo and Adriano de Paula Sabino
Future Pharmacol. 2021, 1(1), 60-79; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010006 - 03 Dec 2021
Viewed by 2640
Abstract
Adenylate kinase 3 (AK3) is an enzyme located in the mitochondrial matrix involved in purine homeostasis. This protein has been considered a potential therapeutic target in chronic lymphocytic leukemia (CLL), because the silencing of the AK3 gene has inhibited cell growth in CLL [...] Read more.
Adenylate kinase 3 (AK3) is an enzyme located in the mitochondrial matrix involved in purine homeostasis. This protein has been considered a potential therapeutic target in chronic lymphocytic leukemia (CLL), because the silencing of the AK3 gene has inhibited cell growth in CLL in vitro models. This study aimed to design potential AK3 inhibitors by applying molecular modeling techniques. Through the mapping of AK3 binding sites, essential interaction fields for pharmacophore design were identified. Online libraries were virtually screened by using a pharmacophore model, and 6891 compounds exhibited the functional groups for interaction with the target. These compounds underwent molecular docking simulations through Surflex and GOLD programs. After visual inspection, we selected 13 compounds for pharmacokinetic properties toxicology prediction via admetSAR and Protox web servers. Finally, six compounds were chosen for further analysis. Full article
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12 pages, 1439 KiB  
Article
Clinical Demonstrations of Controlled-Release Tablets Constructed by the Combined Usage of Shellac and Hydroxypropyl Methylcellulose
by Junichiro Wakamatsu, Kanae Sato, Keisuke Uryu and Isafumi Maru
Future Pharmacol. 2021, 1(1), 48-59; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010005 - 18 Nov 2021
Cited by 2 | Viewed by 3087
Abstract
A new tablet system was examined for an intestinal delivery system using hydroxypropyl methylcellulose (HPMC) and shellac. HPMC was incorporated into the inside of the tablet, and shellac was coated on the surface, which was evaluated for its controlled-release property through several dissolution [...] Read more.
A new tablet system was examined for an intestinal delivery system using hydroxypropyl methylcellulose (HPMC) and shellac. HPMC was incorporated into the inside of the tablet, and shellac was coated on the surface, which was evaluated for its controlled-release property through several dissolution tests, firstly in vitro and then via two kinds of clinical studies with healthy volunteers. The clinical studies were originally designed by employing X-ray photography for the movements of the tablets in the gastrointestinal tract and an electronical device to easily analyze the absorption profile of glucose, a model compound. It was found that the dissolution of the tablet was strongly suppressed in a simulated gastric fluid (pH 1.2) and subsequently started to disintegrate in a simulated intestinal fluid (pH 6.8). The first human study with X-ray photography revealed that the model tablets could pass through the stomach without disintegrating. The controlled release of the tablets was further confirmed via analyses of the AUC, Cmax, and Tmax for the blood glucose concentration with other volunteers. The AUC and Cmax were significantly reduced by using our system, thus concluding that the delivery system combined with the addition of HPMC and a shellac coating unequivocally leads to controlled release in the human gastrointestinal tract. Full article
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7 pages, 1780 KiB  
Communication
An Investigation into the Impact of a Glutaminase Inhibitor, Compound 968, on Nrf2 Signaling
by Wei Lei, Valentin M. Kliebe and Xin Chen
Future Pharmacol. 2021, 1(1), 41-47; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010004 - 18 Nov 2021
Viewed by 2194
Abstract
Glutaminase is a critical enzyme that catalyzes the process of glutaminolysis for energy synthesis. Meanwhile, glutaminase also contributes to the pathological process of various diseases, such as cancer, neurodegenerative diseases, and inflammation. This leads to the discovery of glutaminase inhibitors for therapeutical uses. [...] Read more.
Glutaminase is a critical enzyme that catalyzes the process of glutaminolysis for energy synthesis. Meanwhile, glutaminase also contributes to the pathological process of various diseases, such as cancer, neurodegenerative diseases, and inflammation. This leads to the discovery of glutaminase inhibitors for therapeutical uses. However, the mechanisms of the beneficial therapeutical effect of glutaminase inhibitors are still unclear. This pilot study aimed to determine the impact of a well-characterized glutaminase inhibitor, compound 968 (C968), on Nrf2 signaling. We performed molecular docking, luciferase assay, and quantitative PCR to determine the activation of Nrf2 and the expression of several Nrf2-related genes. These experiments found that C968 induced the Nrf2 activation and promoted the expression of Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H Quinone Dehydrogenase-1 (NQO-1). All findings provide evidence that Nrf2 activation could be one of the mechanisms contributing to the therapeutical activity of C968, but more studies are warranted to further confirm this mechanism. Full article
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14 pages, 1046 KiB  
Systematic Review
Kiwifruit (Actinidia spp.) Dietary Consumption for Constipation: A Systematic Review and Meta-Analysis
by Michele Antonelli and Davide Donelli
Future Pharmacol. 2021, 1(1), 27-40; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010003 - 04 Nov 2021
Cited by 1 | Viewed by 4175
Abstract
The aim of this systematic review is to understand if kiwifruit dietary consumption can effectively improve constipation and intestinal function. PubMed, EMBASE, and Cochrane Library were systematically searched for relevant studies from inception up to September 2021. After database search, nine clinical studies [...] Read more.
The aim of this systematic review is to understand if kiwifruit dietary consumption can effectively improve constipation and intestinal function. PubMed, EMBASE, and Cochrane Library were systematically searched for relevant studies from inception up to September 2021. After database search, nine clinical studies were considered eligible for inclusion. Most trials were characterised by a limited number of study participants (median: 20, min: 11, max: 79) and had a cross-over design. On average, study participants ate from two to four kiwifruits a day for a period varying from three days to four weeks. Included trials almost exclusively involved young or middle-aged adults with a high female-to-male ratio, whereas direct evidence for elderly people (>65 years old) is scant. Moderate quality evidence indicated that kiwifruit dietary consumption can improve complete bowel movements per week and decrease stool consistency in both healthy subjects and patients with constipation due to irritable bowel syndrome, probably owing to the fruit fibre and water content. Kiwifruit dietary consumption can also have beneficial effects beyond intestinal motility, such as a mild anti-inflammatory and antioxidant effect on the gut barrier, due to a combined activity of all its nutrients (enzymes, vitamins, minerals). When only patients affected by constipation were considered, kiwifruit consumption was likely associated with a short-term significant increase in defecation frequency but not always with significant changes in stool consistency. These results were also supported by studies characterised by the highest methodological quality and confirmed by the meta-analysis about the effects of kiwifruit-based interventions on defecation frequency (g = 0.576; 95% CI: (0.174; 0.978); p = 0.012). Further investigations on the topic are recommended to strengthen the consistency of current evidence with larger trials. Full article
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24 pages, 2407 KiB  
Review
Mitochondrial Transplantation: Is It a Feasible Therapy to Prevent the Cardiorenal Side Effects of Cisplatin?
by Isabel Amador-Martínez, Estefani Yaquelin Hernández-Cruz, Alexis Paulina Jiménez-Uribe, Laura Gabriela Sánchez-Lozada, Omar Emiliano Aparicio-Trejo, Edilia Tapia, Jonatan Barrera-Chimal and José Pedraza-Chaverri
Future Pharmacol. 2021, 1(1), 3-26; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010002 - 15 Sep 2021
Cited by 5 | Viewed by 4039
Abstract
Mitochondrial transplantation (MT) is a new experimental approach that has demonstrated positive results reverting mitochondrial alterations in cardiac and kidney dysfunction mainly mediated by oxidative stress. On the other hand, cisplatin is an effective and widely used antineoplastic drug in treating several cancers; [...] Read more.
Mitochondrial transplantation (MT) is a new experimental approach that has demonstrated positive results reverting mitochondrial alterations in cardiac and kidney dysfunction mainly mediated by oxidative stress. On the other hand, cisplatin is an effective and widely used antineoplastic drug in treating several cancers; however, cisplatin has notorious side effects in different organs, such as the heart, kidneys, liver, and brain; the kidney being one of the most affected. The genitourinary system is the principal excretion pathway of cisplatin, since it is removed from the blood primarily by glomerular filtration and tubular secretion, and it may cause a sudden reduction in the renal function (acute kidney injury “AKI”), in part, by inducing mitochondrial dysfunction and the consequent oxidative stress in the tubular segment. In addition, AKI may associate with cardiac alterations, as occurs in acute cardiorenal syndrome. Due to the high prevalence of renal and cardiac side effects produced by cisplatin, here we discuss the possible use of MT as a novel therapy that could protect tissues by alleviating mitochondrial dysfunction and reducing reactive oxygen species (ROS) production. Full article
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2 pages, 276 KiB  
Editorial
The New Future Pharmacology Journal: A Cutting-Edge Opportunity for Rapidly Sharing and Widely Disseminating the Most Advanced Research Ideas and Findings
by Fabrizio Schifano
Future Pharmacol. 2021, 1(1), 1-2; https://0-doi-org.brum.beds.ac.uk/10.3390/futurepharmacol1010001 - 18 Jun 2021
Viewed by 2235
Abstract
The journal Future Pharmacology (ISSN 2673-9879) [...] Full article
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