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Future Pharmacol., Volume 2, Issue 4 (December 2022) – 16 articles

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12 pages, 987 KiB  
Article
Persistence of Second and Third-Line Biologics in Inflammatory Bowel Disease: A Multi-Centre Cohort Study
by Timothy P. Hanrahan, Robbie Chan, Daniel Tassone, Nik S. Ding, Chamara Basnayake, Julien Schulberg, Abhinav Vasudevan, Michael Kamm, Michael De Gregorio, Daniel R. van Langenberg and Ola Niewiadomski
Future Pharmacol. 2022, 2(4), 669-680; https://doi.org/10.3390/futurepharmacol2040041 - 16 Dec 2022
Viewed by 1765
Abstract
Background: Despite proven efficacy of biologics in inflammatory bowel disease (IBD), many exhibit primary non-response or secondary loss of response and switch to subsequent biologic(s). Here, we identified early predictors of second- and/or third-line biologic persistence in IBD, in a real-world cohort of [...] Read more.
Background: Despite proven efficacy of biologics in inflammatory bowel disease (IBD), many exhibit primary non-response or secondary loss of response and switch to subsequent biologic(s). Here, we identified early predictors of second- and/or third-line biologic persistence in IBD, in a real-world cohort of patients. Methods: A retrospective multicentre cohort study was conducted on patients receiving second- and/or third-line biologics for IBD from 2005–2021. Cox regression was applied to identify factors predictive of longer cumulative biologic persistence prior to treatment failure. Results: Of 179 patients who received ≥2 biologics, 159 (88.8%) received an anti-tumour necrosis factor (anti-TNF) first-line. There was a significantly increased likelihood of longer treatment persistence in recipients who received an anti-TNF first, versus those that received a non-anti-TNF agent first (p < 0.01). A diagnosis of CD (OR 7.1, 95% CI [2.3–21.7], p < 0.01), and endoscopic remission achieved on the first biologic (OR 10.4 [1.3–79.9], p = 0.03) were positive predictors of longer biologic persistence, whilst advancing age at IBD diagnosis (OR 0.97 [0.94–0.99], p = 0.04) and primary non-response to initial biologic (OR 0.3 [0.1–0.7], p < 0.01) were inversely associated with biologic persistence. Conclusions: These real-world data demonstrate multiple, simple to identify factors that offer the potential for early objectively assessed response to first-line biologic to predict future biologic persistence. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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9 pages, 566 KiB  
Article
Tramadol Steady-State Pharmacokinetics of Immediate-Release Capsules and Sustained-Release Tablets in Dogs
by Esther Winter, Ingeborg van Geijlswijk, Ies Akkerdaas, Marieke Sturkenboom and Ronette Gehring
Future Pharmacol. 2022, 2(4), 660-668; https://doi.org/10.3390/futurepharmacol2040040 - 10 Dec 2022
Cited by 1 | Viewed by 1945
Abstract
Tramadol is a veterinary analgesic for dogs. In this study, the steady-state pharmacokinetics of a sustained-release (SR) tablet (Tramagetic OD®) and immediate-release capsules (IR) were compared. In a crossover design, six dogs received five doses of IR 50 mg four times [...] Read more.
Tramadol is a veterinary analgesic for dogs. In this study, the steady-state pharmacokinetics of a sustained-release (SR) tablet (Tramagetic OD®) and immediate-release capsules (IR) were compared. In a crossover design, six dogs received five doses of IR 50 mg four times a day (qid), or two doses of SR 200 mg once a day (sid). Eight blood samples were collected per dog, per formulation, up to 6 and 24 h after the last dose, respectively. Serum concentrations of tramadol and its metabolites were measured with LC-MS/MS. Metabolite M1 levels were below the lower limit of quantification (LLOQ) in all samples. The non-compartmental analysis of the time–concentration data showed a later Tmax with the SR formulation (median 6.00 h (3.00–9.00)) and a lower Cmax/D (median 7.74 µg/L/mg/kg (0.09–25.3)) compared to the IR formulation (median Tmax 1.75 h (0.75–2.00) and median Cmax/D 11.1 µg/L/mg/kg (4.8–70.4)). AUCtau/D after SR administration was 55.5 h × kg × µg/L/mg (0–174.1) compared to 29.8 h × kg × µg/L/mg (12.2–140.8) after IR administration. The terminal elimination half-lives were 2.38 h (1.77–6.22) and 1.70 h (0.95–2.11) for the SR and IR formulations, respectively. Strong conclusions cannot be drawn from this study because of the high percentage of samples that were below LLOQ and the great interindividual variability, but these results suggest that Tramagetic OD can be administered less frequently in dogs. Full article
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18 pages, 1669 KiB  
Review
Chasing Uterine Cancer with NK Cell-Based Immunotherapies
by Vijay Kumar, Caitlin Bauer and John H. Stewart IV
Future Pharmacol. 2022, 2(4), 642-659; https://doi.org/10.3390/futurepharmacol2040039 - 9 Dec 2022
Cited by 3 | Viewed by 2257
Abstract
Gynecological cancers, including endometrial adenocarcinoma, significantly contribute to cancer incidence and mortality worldwide. The immune system plays a significant role in endometrial cancer pathogenesis. NK cells, a component of innate immunity, are among the critical innate immune cells in the uterus crucial in [...] Read more.
Gynecological cancers, including endometrial adenocarcinoma, significantly contribute to cancer incidence and mortality worldwide. The immune system plays a significant role in endometrial cancer pathogenesis. NK cells, a component of innate immunity, are among the critical innate immune cells in the uterus crucial in menstruation, embryonic development, and fighting infections. NK cell number and function influence endometrial cancer development and progression. Hence, it becomes crucial to understand the role of local (uterine) NK cells in uterine cancer. Uterine NK (uNK) cells behave differently than their peripheral counterparts; for example, uNK cells are more regulated by sex hormones than peripheral NK cells. A deeper understanding of NK cells in uterine cancer may facilitate the development of NK cell-targeted therapies. This review synthesizes current knowledge on the uterine immune microenvironment and NK cell-targeted uterine cancer therapeutics. Full article
(This article belongs to the Topic Targeting Tumor Metabolism for Cancer Therapy)
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17 pages, 2332 KiB  
Article
Metabolomic Profiling of Red Blood Cells to Identify Molecular Markers of Methotrexate Response in the Collagen Induced Arthritis Mouse Model
by Yezan M. Salamoun, Kishore Polireddy, Yu Kyoung Cho and Ryan Sol Funk
Future Pharmacol. 2022, 2(4), 625-641; https://doi.org/10.3390/futurepharmacol2040038 - 8 Dec 2022
Viewed by 1966
Abstract
Although methotrexate (MTX) is the first line disease-modifying therapy used in the treatment of autoimmune arthritis, it is limited by its unpredictable and variable response profile and lack of therapeutic biomarkers to predict or monitor therapeutic response. The purpose of this work is [...] Read more.
Although methotrexate (MTX) is the first line disease-modifying therapy used in the treatment of autoimmune arthritis, it is limited by its unpredictable and variable response profile and lack of therapeutic biomarkers to predict or monitor therapeutic response. The purpose of this work is to evaluate the utility of red blood cell (RBC) metabolite profiles to screen for molecular biomarkers associated with MTX response. Methods: Utilizing the collagen-induced arthritis mouse model, DBA/1J mice were treated with subcutaneous MTX (20 mg/kg/week) and RBC samples were collected and analyzed by semi-targeted global metabolomic profiling and analyzed by univariate analysis. Results: MTX treatment normalized the following RBC metabolite levels that were found to be altered by disease induction: N-methylisoleucine, nudifloramide, phenylacetylglycine, 1-methyl-L-histidine, PC 42:1, PE 36:4e, PC 42:3, PE 36:4e (16:0e/20:4), and SM d34:0. Changes in the RBC metabolome weakly but significantly correlated with changes in the plasma metabolome following MTX treatment (ρ = 0.24, p = 1.1 × 10−13). The RBC metabolome resulted in the detection of nine significant discriminatory biomarkers, whereas the plasma metabolome resulted in two. Overall, the RBC metabolome yielded more highly sensitive and specific biomarkers of MTX response compared to the plasma metabolome. N-methylisoleucine was found to be highly discriminatory in both plasma and RBCs. Conclusions: Our results suggest that RBCs represent a promising biological matrix for metabolomics and future studies should consider the RBC metabolome in their biomarker discovery strategy. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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17 pages, 692 KiB  
Review
Selenium and Its Compounds in the Treatment of Anxiety and Related Disorders: A Scoping Review of Translational and Clinical Research
by Ravi Philip Rajkumar
Future Pharmacol. 2022, 2(4), 608-624; https://doi.org/10.3390/futurepharmacol2040037 - 6 Dec 2022
Cited by 1 | Viewed by 5836
Abstract
Anxiety disorders are among the most common mental disorders worldwide and often respond incompletely to existing treatments. Selenium, a micronutrient that is a component of several biologically active selenoproteins, is also involved in several aspects of brain functioning and may exert antidepressant and [...] Read more.
Anxiety disorders are among the most common mental disorders worldwide and often respond incompletely to existing treatments. Selenium, a micronutrient that is a component of several biologically active selenoproteins, is also involved in several aspects of brain functioning and may exert antidepressant and anxiolytic effects through multiple pathways. The current paper is a scoping review of translational, observational, and interventional evidence on the potential role of selenium and its compounds in the management of anxiety and related disorders. Evidence from animal models suggests that this approach may be promising. Though evidence from observational studies in humans is inconsistent and affected by several confounding factors, the available evidence from randomized controlled trials suggests that selenium supplementation may be beneficial in the management of certain anxiety-related conditions, such as anxiety in medically ill patients, prevention of anxiety following exposure to traumatic stress, and obsessive-compulsive disorder. This paper provides a critical evaluation of the existing evidence base, including unanswered questions that could serve as the focus of further research, and outlines the potential benefits and risks associated with the use of selenium in anxiety disorders. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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13 pages, 904 KiB  
Review
Selenium-Based Drug Development for Antioxidant and Anticancer Activity
by Sashi Debnath, Abhijeet Agarwal, Neha R. Kumar and Anjan Bedi
Future Pharmacol. 2022, 2(4), 595-607; https://doi.org/10.3390/futurepharmacol2040036 - 6 Dec 2022
Cited by 13 | Viewed by 2525
Abstract
Selenium is one of the eight necessary trace elements humans require for active health balance. It contributes in several ways to the proper functioning of selenoprotein. Selenium has received enormous interest recently due to its therapeutic potential against a number of ailments. To [...] Read more.
Selenium is one of the eight necessary trace elements humans require for active health balance. It contributes in several ways to the proper functioning of selenoprotein. Selenium has received enormous interest recently due to its therapeutic potential against a number of ailments. To date, numerous chemical compounds containing selenium have been investigated for the therapy of cancer and other disorders. Unifying the selenium atom into chemical components (typically organic) greatly increased their bioactivities. We foresee that the structure–property relationship of recently developed materials could significantly decrease the laborious work of background research to achieve target-oriented drug design in coming years. This review summarizes the research progress in the last 10 to 15 years and the application of selenium-containing compounds in the design and synthesis of those materials for potential antioxidant and anticancer agents. Full article
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16 pages, 294 KiB  
Review
Potentially Remediable Shortcomings in the Contemporary Drug Treatment of Migraine
by Mervyn Eadie
Future Pharmacol. 2022, 2(4), 579-594; https://doi.org/10.3390/futurepharmacol2040035 - 22 Nov 2022
Viewed by 1203
Abstract
Despite the availability over the past decade of a number of new pharmaceutical agents with different mechanisms of action from those of the drugs used previously, the contemporary drug therapy of migraine attacks falls rather short of what would be desirable, while the [...] Read more.
Despite the availability over the past decade of a number of new pharmaceutical agents with different mechanisms of action from those of the drugs used previously, the contemporary drug therapy of migraine attacks falls rather short of what would be desirable, while the pharmacological attempt to prevent further attacks appears to prove unsatisfactory about as often as it is successful. The present paper explores reasons for these shortcomings in both the earlier and the current drug therapy of the disorder. Significant major contributory factors appear to be an incomplete understanding of the underlying pathogenic mechanisms of the various stages of the migraine attack, less than optimal pharmacokinetic characteristics of many of the drugs used, and migraine sufferers failing to employ the available drugs to their best advantage. New drugs developed in the light of a more complete understanding of the molecular basis of migraine pathogenesis, together with awareness of pharmacokinetic desiderata in relation to treating and preventing migraine attacks, may go some way towards remedying the situation, but patient decision making may prove more difficult to modify. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
21 pages, 6629 KiB  
Article
Computational Screening of Plant-Derived Natural Products against SARS-CoV-2 Variants
by Waseem Ahmad Ansari, Mohd Aamish Khan, Fahmina Rizvi, Kajim Ali, Mohd Kamil Hussain, Mohammad Saquib and Mohammad Faheem Khan
Future Pharmacol. 2022, 2(4), 558-578; https://doi.org/10.3390/futurepharmacol2040034 - 19 Nov 2022
Cited by 6 | Viewed by 2078
Abstract
The present study explores the efficacy of plant-derived natural products (PDNPs) against spike glycoproteins (S-glycoprotein) of SARS-CoV-2 variants using molecular docking, ADMET, molecular dynamics (MD) simulation and density-functional theory (DFT) analysis. In all, 100 PDNPs were screened against spike glycoprotein of SARS-CoV-2 variants, [...] Read more.
The present study explores the efficacy of plant-derived natural products (PDNPs) against spike glycoproteins (S-glycoprotein) of SARS-CoV-2 variants using molecular docking, ADMET, molecular dynamics (MD) simulation and density-functional theory (DFT) analysis. In all, 100 PDNPs were screened against spike glycoprotein of SARS-CoV-2 variants, namely alpha (B.1.1.17), beta (B.1.351), delta (B.1.617), gamma (P.1) and omicron (B.1.1.529). Results showed that rutin, EGCG, hesperidin, withanolide G, rosmarinic acid, diosmetin, myricetin, epicatechin and quercetin were the top hit compounds against each of the SARS-CoV-2 variants. The most active compounds, rutin, hesperidin, EGCG and rosmarinic acid gave binding scores of −10.2, −8.1, −8.9, −8.3 and −9.2 kcal/mol, against omicron, delta, alpha, beta and gamma variants, respectively. Further, the stability of docked complexes was confirmed by the analysis of molecular descriptors (RMSD, RMSF, SASA, Rg and H-bonds) in molecular dynamic simulation analysis. Moreover, the physiochemical properties and drug-likeness of the tested compounds showed that they have no toxicity or carcinogenicity and may be used as druggable targets. In addition, the DFT study revealed the higher activity of the tested compounds against the target proteins. This led us to conclude that rutin, hesperidin, EGCG and rosmarinic acid are good candidates to target the S-glycoproteins of SARS-CoV-2 variants. Further, in vivo and clinical studies needed to develop them as drug leads against existing or new SARS-CoV-2 variants are currently underway in our laboratory. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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11 pages, 2424 KiB  
Article
Ameliorative Effects of Beetroot Juice Supplementation on Monocrotaline-Induced Pulmonary Hypertension in Rats
by Masashi Tawa, Junya Nagano, Junpei Kitama, Shunto Abe, Ako Fujita, Keisuke Nakagawa and Mamoru Ohkita
Future Pharmacol. 2022, 2(4), 547-557; https://doi.org/10.3390/futurepharmacol2040033 - 16 Nov 2022
Cited by 2 | Viewed by 1745
Abstract
Beetroot is a nitrate-rich vegetable with cardiovascular benefits. This study examined whether ingestion of beetroot juice (BRJ) protects against pulmonary hypertension (PH). Rats were injected subcutaneously with 60 mg/kg monocrotaline (MCT) and randomized to receive either drinking water, low-dose BRJ (BRJ-L, nitrate content: [...] Read more.
Beetroot is a nitrate-rich vegetable with cardiovascular benefits. This study examined whether ingestion of beetroot juice (BRJ) protects against pulmonary hypertension (PH). Rats were injected subcutaneously with 60 mg/kg monocrotaline (MCT) and randomized to receive either drinking water, low-dose BRJ (BRJ-L, nitrate content: 1.4 mmol/L), or high-dose BRJ (BRJ-H, nitrate content: 3.5 mmol/L), which was started 1 week after MCT injection and continued until the end of the experiment. Four weeks after MCT injection, right ventricle (RV) hypertrophy, right ventricular systolic pressure (RVSP) elevation, and pulmonary vascular remodeling were observed. These PH symptoms were less severe in rats supplemented with BRJ-L (Fulton index, p = 0.07; RVSP, p = 0.09, pulmonary arterial medial thickening, p < 0.05), and the beneficial effects were more pronounced than those of BRJ-H supplementation. Plasma and RV nitrite and nitrate levels did not change significantly, even when BRJ-L and BRJ-H were administered. There were no differences in plasma thiobarbituric acid reactive substances (TBARS), a biomarker of oxidative stress, among the groups. BRJ-L supplementation significantly decreased RV TBARS levels compared to MCT alone (p < 0.05), whereas BRJ-H supplementation did not. These findings suggest that starting BRJ supplementation from an early stage of PH ameliorates disease severity, at least partly through the inhibition of local oxidative stress. Habitual ingestion of BRJ may be useful for the management of PH. Full article
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36 pages, 3371 KiB  
Review
A Mechanistic Insight on Phytoconstituents Delivering Hypoglycemic Activity: A Comprehensive Overview
by Shraddha Singh Raghav, Bhavna Kumar, Neeraj Kumar Sethiya and Ankur Kaul
Future Pharmacol. 2022, 2(4), 511-546; https://doi.org/10.3390/futurepharmacol2040032 - 9 Nov 2022
Cited by 4 | Viewed by 3626
Abstract
Diabetes is a long-term (chronic), challenging lifestyle (metabolic) disorder in which the body cannot regulate the amount of sugar in the blood and majorly affecting endocrine system and metabolic functions. Its complications majorly affect the neurons (as developing neuropathy), kidney (as nephropathy), and [...] Read more.
Diabetes is a long-term (chronic), challenging lifestyle (metabolic) disorder in which the body cannot regulate the amount of sugar in the blood and majorly affecting endocrine system and metabolic functions. Its complications majorly affect the neurons (as developing neuropathy), kidney (as nephropathy), and eye (as retinopathy). Diabetes also results in other associated problems, such as diabetic foot ulcers, sexual dysfunction, heart diseases etc. In the traditional medicines, the search for effective hypoglycemic agents is a continuous and challenging approach. Plant-derived bioactives, including alkaloids, phenols, glycosides, anthocyanins, flavonoids, saponins, tannins, polysaccharides, and terpenes, have been established to target cellular and molecular mechanisms involved in carbohydrate metabolism. Numerous diabetic patients select the herbal or traditional medicine system as an alternative therapeutic approach along with the mainstream anti-diabetic drugs. However, due to restrictive hurdles related to solubility and bioavailability, the bioactive compound cannot deliver the requisite effect. In this review, information is presented concerning well researched phytoconstituents established as potential hypoglycemic agents for the prevention and treatment of diabetes and its associated disorders having restricted solubility and bioavailability related issues. This information can be further utilized in future to develop several value added formulation and nutraceutical products to achieve the desired safety and efficacy for the prevention and treatment of diabetes and its related diseases. Full article
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12 pages, 995 KiB  
Article
Effect of Etanercept on Plasmodium yoelii MDR-Induced Liver Lipid Infiltration
by Bhavana Singh Chauhan, Sarika Gunjan, Sunil Kumar Singh, Swaroop Kumar Pandey and Renu Tripathi
Future Pharmacol. 2022, 2(4), 499-510; https://doi.org/10.3390/futurepharmacol2040031 - 7 Nov 2022
Cited by 1 | Viewed by 1243
Abstract
The lipid is a vital metabolic and structural component of the malaria parasite. Malaria parasite-induced liver lipid deposits undergo peroxidation, which ultimately causes tissue damage and histopathological changes, which further lead to many complications. Therefore, it is essential to focus on the factors [...] Read more.
The lipid is a vital metabolic and structural component of the malaria parasite. Malaria parasite-induced liver lipid deposits undergo peroxidation, which ultimately causes tissue damage and histopathological changes, which further lead to many complications. Therefore, it is essential to focus on the factors responsible for this stimulated lipid accumulation during malaria infection. In the present study, we have correlated the significant increase in serum TNF-α and liver triglyceride during Plasmodium yoelii MDR infection in mice. In order to explore the role of TNF-α in inducing lipid accumulation in the liver during malaria infection, we have used a competitive TNF-α inhibitor Etanercept, for the treatment of Plasmodium yoelii MDR (Py MDR) infected mice and found that Etanercept displayed up to a three-fold inhibition of the liver triglyceride level in Py MDR infected mice. These results were also confirmed by triglyceride specific oil red O staining of liver sections. In addition, all the treatment groups also showed inhibition in the level of serum TNF-α and the liver malondialdehyde (MDA), a byproduct of lipid peroxidation. Our study thus concludes that Etanercept significantly reduces Plasmodium-induced liver triglyceride and further saves the host liver from malaria-induced lipid infiltration and liver damage. Therefore, treatment with Etanercept, along with a standard antimalarial, may prove a better therapy for the disease. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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39 pages, 3464 KiB  
Review
Preventing Microbial Infections with Natural Phenolic Compounds
by Kardelen Ecevit, Alexandre A. Barros, Joana M. Silva and Rui L. Reis
Future Pharmacol. 2022, 2(4), 460-498; https://doi.org/10.3390/futurepharmacol2040030 - 2 Nov 2022
Cited by 32 | Viewed by 7572
Abstract
The struggle between humans and pathogens has taken and is continuing to take countless lives every year. As the misusage of conventional antibiotics increases, the complexity associated with the resistance mechanisms of pathogens has been evolving into gradually more clever mechanisms, diminishing the [...] Read more.
The struggle between humans and pathogens has taken and is continuing to take countless lives every year. As the misusage of conventional antibiotics increases, the complexity associated with the resistance mechanisms of pathogens has been evolving into gradually more clever mechanisms, diminishing the effectiveness of antibiotics. Hence, there is a growing interest in discovering novel and reliable therapeutics able to struggle with the infection, circumvent the resistance and defend the natural microbiome. In this regard, nature-derived phenolic compounds are gaining considerable attention due to their potential safety and therapeutic effect. Phenolic compounds comprise numerous and widely distributed groups with different biological activities attributed mainly to their structure. Investigations have revealed that phenolic compounds from natural sources exhibit potent antimicrobial activity against various clinically relevant pathogens associated with microbial infection and sensitize multi-drug resistance strains to bactericidal or bacteriostatic antibiotics. This review outlines the current knowledge about the antimicrobial activity of phenolic compounds from various natural sources, with a particular focus on the structure-activity relationship and mechanisms of actions of each class of natural phenolic compounds, including simple phenols, phenolic acids, coumarin, flavonoids, tannins, stilbenes, lignans, quinones, and curcuminoids. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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16 pages, 2372 KiB  
Article
Macrophage Delivered HSV1716 Is Active against Triple Negative Breast Cancer
by Amy Kwan, Faith Howard, Natalie Winder, Emer Atkinson, Ameera Jailani, Priya B. Patel, Richard Allen, Penelope D. Ottewell, Gary C. Shaw, Joe Conner, Caroline Wilson, Sanjay K. Srivastava, Sarah J. Danson, Claire Lewis, Janet E. Brown and Munitta Muthana
Future Pharmacol. 2022, 2(4), 444-459; https://doi.org/10.3390/futurepharmacol2040029 - 21 Oct 2022
Viewed by 2901
Abstract
Oncolytic viruses (OV) promote anti-tumour responses through the initiation of immunogenic cancer cell death which activates the host’s systemic anti-tumour immunity. We have previously shown that intravenously administered HSV1716 is an effective treatment for mammary cancer. However, intravenous administration of a virus has [...] Read more.
Oncolytic viruses (OV) promote anti-tumour responses through the initiation of immunogenic cancer cell death which activates the host’s systemic anti-tumour immunity. We have previously shown that intravenously administered HSV1716 is an effective treatment for mammary cancer. However, intravenous administration of a virus has the potential to result in neutralization and sequestration of the virus which may reduce efficacy. Here, we show that the oncolytic virus HSV1716 can be administered within a cellular carrier (macrophages). PyMT and 4T1 murine mammary cancer cell lines were implanted into immuno-competent murine models (orthotopic primary, early metastatic and brain metastasis models). HSV1716 or macrophages armed with HSV1716 (M-HSV1716) were administered intravenously, and tumour size was quantified using caliper measurement or bioluminescence imaging. Administration of M-HSV1716 led to tumour shrinkage and increased the survival of animals. Furthermore, these results were achieved with a 100-fold lower viral load, which has the potential for decreased toxicity. Our results demonstrate that M-HSV1716 is associated with activity against murine mammary cancers and provides an alternative platform for the systemic delivery of OV. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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13 pages, 331 KiB  
Review
A Critical Review of Chloroquine and Hydroxychloroquine as Potential Adjuvant Agents for Treating People with Cancer
by Amal Kamal Abdel-Aziz, Mona Kamal Saadeldin, Ahmed Hamed Salem, Safaa A. Ibrahim, Samia Shouman, Ashraf B. Abdel-Naim and Roberto Orecchia
Future Pharmacol. 2022, 2(4), 431-443; https://doi.org/10.3390/futurepharmacol2040028 - 18 Oct 2022
Cited by 6 | Viewed by 4864
Abstract
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used to treat malaria and autoimmune diseases for more than 70 years; they also have immunomodulatory and anticancer effects, which are linked to autophagy and autophagy-independent mechanisms. Herein, we review the pharmacokinetics, preclinical studies and clinical [...] Read more.
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used to treat malaria and autoimmune diseases for more than 70 years; they also have immunomodulatory and anticancer effects, which are linked to autophagy and autophagy-independent mechanisms. Herein, we review the pharmacokinetics, preclinical studies and clinical trials investigating the use of CQ and HCQ as adjuvant agents in cancer therapy. We also discuss their safety profile, drug–drug and drug–disease interactions. Systematic studies are required to define the use of CQ/HCQ and/or their analogues in cancer treatment and to identify predictive biomarkers of responder subpopulations. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
16 pages, 1108 KiB  
Review
Dendrimers-Based Drug Delivery System: A Novel Approach in Addressing Parkinson’s Disease
by Michaella B. Ordonio, Randa Mohammed Zaki and Amal Ali Elkordy
Future Pharmacol. 2022, 2(4), 415-430; https://doi.org/10.3390/futurepharmacol2040027 - 10 Oct 2022
Cited by 2 | Viewed by 2095
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disease that is characterized by the loss of dopamine. Since dopamine has trouble entering the blood–brain barrier, the utilization of dendrimers and other nanomaterials is considered for conjugating the neurotransmitter and other PD drugs. Dendrimers are [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disease that is characterized by the loss of dopamine. Since dopamine has trouble entering the blood–brain barrier, the utilization of dendrimers and other nanomaterials is considered for conjugating the neurotransmitter and other PD drugs. Dendrimers are three-dimensional, hyper-branched structures that are categorized into several generations. Alpha-synuclein (ASN) is the protein involved in regulating dopaminergic functions and is the main aggregate found inside Lewy bodies. Different types of dendrimers have shown efficacy in disrupting the formation of unstable beta structures of ASN and fibrillation. The conjugation of PD drugs into nanomaterials has elicited a prolonged duration of action and sustained release of the drugs inside the BBB. The objectives of this study are to review the applications of a dendrimer-based drug delivery system in addressing the root cause of Parkinson’s disease and to emphasize the delivery of anti-Parkinson’s drugs such as rotigotine, pramipexole and dopamine using routes of administration other than oral and intravenous. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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38 pages, 3069 KiB  
Review
Implications and Practical Applications of the Chemical Speciation of Iodine in the Biological Context
by Astrid N. Espino-Vázquez, Flor C. Rojas-Castro and Liria Mitzuko Fajardo-Yamamoto
Future Pharmacol. 2022, 2(4), 377-414; https://doi.org/10.3390/futurepharmacol2040026 - 3 Oct 2022
Cited by 2 | Viewed by 4148
Abstract
Iodine is a highly reactive element with a single natural and stable isotopic form (127I). In the biosphere, it is one of the 30 essential elements for life, and its chemical speciation defines its availability and biological activities. The most relevant [...] Read more.
Iodine is a highly reactive element with a single natural and stable isotopic form (127I). In the biosphere, it is one of the 30 essential elements for life, and its chemical speciation defines its availability and biological activities. The most relevant chemical species are iodate (IO3) and iodide (I) as the major sources of iodine, with molecular iodine (I2) and hypoiodous acid (HIO) as the most reactive species, and thyroid hormones (THs) as the representative organic compounds. In human biology, THs are master regulators of metabolism, while inorganic species serve for the iodination of organic molecules and contribute to the innate immune system and the antioxidant cellular defense. Additionally, I, I2, δ-lactone (6-IL), and α-iodohexadecanal (α-IHDA) have shown therapeutic potential in counteracting oxidative stress, cancer, and inflammation. Both inorganic and organic species have applications in the health science industry, from the manufacturing of disinfection and wound care products to supplements, medicines, and contrast media for radiography. Even after nuclear disasters, intake of high doses of iodine prevents the accumulation of radioactive iodine in the body. Conversely, the controlled production of iodine radioisotopes such as 123I, 124I, 125I, and 131I is exploited in nuclear medicine for radiotherapy and diagnostics. Full article
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