Journal Description
Pharmaceuticals
Pharmaceuticals
is a peer-reviewed, open access journal of medicinal chemistry and related drug sciences, published monthly online by MDPI. The Academy of Pharmaceutical Sciences (APS) is partners of Pharmaceuticals and their members receive a discount on the article processing charge.
- Open Access free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Pharmacology & Pharmacy) / CiteScore - Q2 (Pharmaceutical Science)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.6 days after submission; acceptance to publication is undertaken in 3.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about Pharmaceuticals.
- International Electronic Conference on Medicinal Chemistry (https://sciforum.net/series/ecmc/latest)
- Companion journals for Pharmaceuticals include: Pharmacoepidemiology, Psychoactives and Drugs and Drug Candidates.
Impact Factor:
4.6 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Amber (Succinite) Extract Enhances Glucose Uptake through the Up-Regulation of ATP and Down-Regulation of ROS in Mouse C2C12 Cells
Pharmaceuticals 2024, 17(5), 586; https://doi.org/10.3390/ph17050586 - 03 May 2024
Abstract
Traditionally, amber (Succinite) has been used to alleviate all types of pain, skin allergies, and headaches. However, no studies have been conducted on its antidiabetic and antioxidant effects. In this study, differentiated skeletal muscle C2C12 cells were used to demonstrate the protective effects
[...] Read more.
Traditionally, amber (Succinite) has been used to alleviate all types of pain, skin allergies, and headaches. However, no studies have been conducted on its antidiabetic and antioxidant effects. In this study, differentiated skeletal muscle C2C12 cells were used to demonstrate the protective effects of amber (AMB) against H2O2-induced cell death. In addition, the effects of AMB on glucose uptake and ATP production were investigated. Our results showed that AMB at 10, 25, and 50 μg/mL suppressed the elevation of ROS production induced by H2O2 in a dose-dependent manner. Moreover, AMB enhanced glucose utilization in C2C12 cells through the improvement of ATP production and an increase in PGC-1α gene expression resulting in an amelioration of mitochondrial activity. On the other hand, AMB significantly increased the gene expression of glucose transporters GLUT4 and GLUT1. Our finding suggests that AMB can be used as a natural supplement for diabetes treatment and for the promotion of skeletal muscle function.
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(This article belongs to the Section Pharmacology)
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Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival
by
Soheila Ali Akbari Ghavimi, Trent J. Faulkner, Rama Rao Tata, August J. Hemmerla, Samantha E. Huddleston, Farnoushsadat Rezaei, Ethan S. Lungren, Rui Zhang, Erin E. Bumann and Bret D. Ulery
Pharmaceuticals 2024, 17(5), 585; https://doi.org/10.3390/ph17050585 - 02 May 2024
Abstract
Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be
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Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca2+/Pi concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing H2S donor, were applied to assess the influence of H2S on MSC proliferation. The results suggested a toxicity limit of 4 mM for NaSH and that 1 mM of NaSH could improve cell proliferation and differentiation in the presence of cytotoxic levels of Ca2+ (32 mM) and/or Pi (16 mM). To controllably deliver H2S over time, a novel donor molecule (thioglutamic acid—GluSH) was synthesized and evaluated for its H2S release profile. Excitingly, GluSH successfully maintained cytoprotective level of H2S over 7 days. Furthermore, MSCs exposed to cytotoxic Ca2+/Pi concentrations in the presence of GluSH were able to thrive and differentiate into osteoblasts. These findings suggest that the incorporation of a sustained H2S donor such as GluSH into CaP-based bone graft substitutes can facilitate considerable cytoprotection, making it an attractive option for complex bone regenerative engineering applications.
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(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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Open AccessArticle
Structural Modification and Optimisation of Hyperoside Oriented to Inhibit TGF-β-Induced EMT Activity in Alveolar Epithelial Cells
by
Ziye Gao, Mengzhen Xu, Chuanguo Liu, Kai Gong, Xin Yu, Kaihui Lu, Jiang Zhu, Haixing Guan and Qingjun Zhu
Pharmaceuticals 2024, 17(5), 584; https://doi.org/10.3390/ph17050584 - 02 May 2024
Abstract
Pulmonary fibrosis (PF) is a disease characterised by diffuse nonspecific alveolar inflammation with interstitial fibrosis, which clinically manifests as dyspnoea and a significant decline in lung function. Many studies have shown that the epithelial–mesenchymal transition (EMT) plays a pivotal role in the pathogenesis
[...] Read more.
Pulmonary fibrosis (PF) is a disease characterised by diffuse nonspecific alveolar inflammation with interstitial fibrosis, which clinically manifests as dyspnoea and a significant decline in lung function. Many studies have shown that the epithelial–mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of pulmonary fibrosis. Based on our previous findings, hypericin (Hyp) can effectively inhibit the process of the EMT to attenuate lung fibrosis. Therefore, a series of hyperoside derivatives were synthesised via modifying the structure of hyperoside, and subsequently evaluated for A549 cytotoxicity. Among these, the pre-screening of eight derivatives inhibits the EMT. In this study, we evaluated the efficacy of Z6, the most promising hyperoside derivative, in reversing TGF-β1-induced EMTs and inhibiting the EMT-associated migration of A549 cells. After the treatment of A549 cells with Z6 for 48 h, RT-qPCR and Western blot results showed that Z6 inhibited TGF-β1-induced EMTs in epithelial cells by supressing morphological changes in A549 cells, up-regulating E-cadherin (p < 0.01, p < 0.001), and down-regulating Vimentin (p < 0.01, p < 0.001). This treatment significantly reduced the mobility of transforming growth factor β1 (TGF-β1)-stimulated cells (p < 0.001) as assessed by wound closure, while increasing the adhesion rate of A549 cells (p < 0.001). In conclusion, our results suggest that hyperoside derivatives, especially compound Z6, are promising as potential lead compounds for treating pulmonary fibrosis, and therefore deserve further investigation.
Full article
(This article belongs to the Section Pharmacology)
Open AccessArticle
Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage
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Thomas W. Chu, Ching-Chih Ho, Yu-Jou Hsu, Yuan-Hsin Lo, Nan-Lin Wu, Yuan-Bin Cheng, Mao-Xuan Hong, Der-Chen Chang and Chi-Feng Hung
Pharmaceuticals 2024, 17(5), 583; https://doi.org/10.3390/ph17050583 - 02 May 2024
Abstract
The ancient Chinese medical book “Compendium of Materia Medica” records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus
[...] Read more.
The ancient Chinese medical book “Compendium of Materia Medica” records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1β, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.
Full article
(This article belongs to the Section Biopharmaceuticals)
Open AccessArticle
Evaluation of the Efficacy of OSU-2S in the Treatment of Non-Small-Cell Lung Cancer and Screening of Potential Targets of Action
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Mengyuan Han, Xiangran Liu, Sendaer Hailati, Nurbiya Nurahmat, Dilihuma Dilimulati, Alhar Baishan, Alifeiye Aikebaier and Wenting Zhou
Pharmaceuticals 2024, 17(5), 582; https://doi.org/10.3390/ph17050582 - 01 May 2024
Abstract
(1) Background: OSU-2S is a derivative of FTY720 and exhibits significant inhibitory effects on various cancer cells. There is currently no research on the mechanism of the impact of OSU-2S on NSCLC development. We analysed and validated the hub genes and pharmacodynamic effects
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(1) Background: OSU-2S is a derivative of FTY720 and exhibits significant inhibitory effects on various cancer cells. There is currently no research on the mechanism of the impact of OSU-2S on NSCLC development. We analysed and validated the hub genes and pharmacodynamic effects of OSU-2S to treat NSCLC. (2) Methods: The hub genes of OSU-2S for the treatment of NSCLC were screened in PharmMapper, genecard, and KM Plotter database by survival and expression analysis. The effect of OSU-2S on hub gene expression was verified by Western blot analysis. The ex vivo and in vivo efficacy of OSU-2S on tumour growth was verified using A549 cells and a xenografted animal model. (3) Results: A total of 7 marker genes for OSU-2S treatment of NSCLC were obtained. AURKA and S1PR1 were screened as hub genes. Significant differences in the expression of AURKA and S1PR1 between normal and lung adenocarcinoma (LUAD) tissues were found in the GEPIA2 database; Western blot showed that OSU-2S could affect p-AURKA and S1PR1 protein expression. OSU-2S significantly inhibited tumour growth in A549 cells and xenografted animal models. (4) Conclusions: Our study confirms the inhibitory effect of OSU-2S on NSCLC, screens and demonstrates its potential targets AURKA(p-AURKA) and S1PR1, and provides a research basis for treating NSCLC with OSU-2S.
Full article
(This article belongs to the Topic Research in Pharmacological Therapies)
Open AccessArticle
Investigating the Antiviral Properties of Nyctanthes arbor-tristis Linn against the Ebola, SARS-CoV-2, Nipah, and Chikungunya Viruses: A Computational Simulation Study
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Raed Albiheyri, Varish Ahmad, Mohammad Imran Khan, Faisal A. Alzahrani and Qazi Mohammad Sajid Jamal
Pharmaceuticals 2024, 17(5), 581; https://doi.org/10.3390/ph17050581 - 30 Apr 2024
Abstract
Background: The hunt for naturally occurring antiviral compounds to combat viral infection was expedited when COVID-19 and Ebola spread rapidly. Phytochemicals from Nyctanthes arbor-tristis Linn were evaluated as significant inhibitors of these viruses. Methods: Computational tools and techniques were used to assess the
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Background: The hunt for naturally occurring antiviral compounds to combat viral infection was expedited when COVID-19 and Ebola spread rapidly. Phytochemicals from Nyctanthes arbor-tristis Linn were evaluated as significant inhibitors of these viruses. Methods: Computational tools and techniques were used to assess the binding pattern of phytochemicals from Nyctanthes arbor-tristis Linn to Ebola virus VP35, SARS-CoV-2 protease, Nipah virus glycoprotein, and chikungunya virus. Results: Virtual screening and AutoDock analysis revealed that arborside-C, beta amyrin, and beta-sitosterol exhibited a substantial binding affinity for specific viral targets. The arborside-C and beta-sitosterol molecules were shown to have binding energies of −8.65 and −9.11 kcal/mol, respectively, when interacting with the major protease. Simultaneously, the medication remdesivir exhibited a control value of −6.18 kcal/mol. The measured affinity of phytochemicals for the other investigated targets was −7.52 for beta-amyrin against Ebola and −6.33 kcal/mol for nicotiflorin against Nipah virus targets. Additional molecular dynamics simulation (MDS) conducted on the molecules with significant antiviral potential, specifically the beta-amyrin-VP35 complex showing a stable RMSD pattern, yielded encouraging outcomes. Conclusions: Arborside-C, beta-sitosterol, beta-amyrin, and nicotiflorin could be established as excellent natural antiviral compounds derived from Nyctanthes arbor-tristis Linn. The virus-suppressing phytochemicals in this plant make it a compelling target for both in vitro and in vivo research in the future.
Full article
(This article belongs to the Special Issue Antiviral Agents, 2024)
Open AccessArticle
1H-NMR Metabolomic Study of the Mushroom Pleurotus djamor for the Identification of Nematocidal Compounds
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Jesús Antonio Pineda-Alegría, Luis Manuel Peña-Rodríguez, Alexandre Cardoso-Taketa, José E. Sánchez, Juan Felipe de Jesús Torres-Acosta, Gloria Ivonne Hernández-Bolio, Anabel Ortiz-Caltempa, María Luisa Villarreal and Liliana Aguilar-Marcelino
Pharmaceuticals 2024, 17(5), 580; https://doi.org/10.3390/ph17050580 - 30 Apr 2024
Abstract
Due to the increasing populations of anthelmintic-resistant gastrointestinal nematodes and as a consequence of the adverse effects of synthetic drugs, this study focuses on the search for secondary metabolites with nematocidal activity from the edible mushroom Pleurotus djamor using The proton nuclear magnetic
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Due to the increasing populations of anthelmintic-resistant gastrointestinal nematodes and as a consequence of the adverse effects of synthetic drugs, this study focuses on the search for secondary metabolites with nematocidal activity from the edible mushroom Pleurotus djamor using The proton nuclear magnetic resonance (1H-NMR) metabolomics. The highest activity was shown by the ethyl acetate fractions of mycelium (EC50 290.8 µg/mL) and basidiomes (EC50 282.7 µg/mL). Principal component analysis (PCA) and hierarchical data analysis (HCA) of the 1H-NMR metabolic profiles data showed that the ethanolic extracts, the ethyl acetate, butanol, and water fractions from mycelium have different metabolic profiles than those from basidiomes, while low polarity (hexane) fractions from both stages of fungal development show similar profiles. Orthogonal partial least squares discriminant analysis (OPLS-DA) allowed the identification of signals in the 1H-NMR metabolic profile associated with nematocidal activity. The signals yielded via OPLS-DA and bidimensional NMR analysis allowed the identification of uracil as a component in the ethyl acetate fraction from basidiomes, with an EC50 of 237.7 µg/mL. The results obtained showed that chemometric analyses of the 1H-NMR metabolic profiles represent a viable strategy for the identification of bioactive compounds from samples with complex chemical profiles.
Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
Open AccessArticle
The Impact of A3AR Antagonism on the Differential Expression of Chemoresistance-Related Genes in Glioblastoma Stem-like Cells
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Liuba Peñate, Diego Carrillo-Beltrán, Carlos Spichiger, Alexei Cuevas-Zhbankova, Ángelo Torres-Arévalo, Pamela Silva, Hans G. Richter, Ángel Ayuso-Sacido, Rody San Martín and Claudia Quezada-Monrás
Pharmaceuticals 2024, 17(5), 579; https://doi.org/10.3390/ph17050579 - 30 Apr 2024
Abstract
Glioblastoma (GB) is the most aggressive and common primary malignant tumor of the brain and central nervous system. Without treatment, the average patient survival time is about six months, which can be extended to fifteen months with multimodal therapies. The chemoresistance observed in
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Glioblastoma (GB) is the most aggressive and common primary malignant tumor of the brain and central nervous system. Without treatment, the average patient survival time is about six months, which can be extended to fifteen months with multimodal therapies. The chemoresistance observed in GB is, in part, attributed to the presence of a subpopulation of glioblastoma-like stem cells (GSCs) that are characterized by heightened tumorigenic capacity and chemoresistance. GSCs are situated in hypoxic tumor niches, where they sustain and promote the stem-like phenotype and have also been correlated with high chemoresistance. GSCs have the particularity of generating high levels of extracellular adenosine (ADO), which causes the activation of the A3 adenosine receptor (A3AR) with a consequent increase in the expression and activity of genes related to chemoresistance. Therefore, targeting its components is a promising alternative for treating GB. This analysis determined genes that were up- and downregulated due to A3AR blockades under both normoxic and hypoxic conditions. In addition, possible candidates associated with chemoresistance that were positively regulated by hypoxia and negatively regulated by A3AR blockades in the same condition were analyzed. We detected three potential candidate genes that were regulated by the A3AR antagonist MRS1220 under hypoxic conditions: LIMD1, TRIB2, and TGFB1. Finally, the selected markers were correlated with hypoxia-inducible genes and with the expression of adenosine-producing ectonucleotidases. In conclusion, we detected that hypoxic conditions generate extensive differential gene expression in GSCs, increasing the expression of genes associated with chemoresistance. Furthermore, we observed that MRS1220 could regulate the expression of LIMD1, TRIB2, and TGFB1, which are involved in chemoresistance and correlate with a poor prognosis, hypoxia, and purinergic signaling.
Full article
(This article belongs to the Special Issue Purinergic Receptors and Ectonucleotidases as Novel Therapeutic Targets)
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Open AccessReview
Anticancer Potential and Molecular Targets of Pristimerin in Human Malignancies
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Kirti S. Prabhu, Serah Jessy, Shilpa Kuttikrishnan, Farina Mujeeb, Zahwa Mariyam, Ummu Habeeba, Nuha Ahamad, Ajaz A. Bhat and Shahab Uddin
Pharmaceuticals 2024, 17(5), 578; https://doi.org/10.3390/ph17050578 - 30 Apr 2024
Abstract
The growing global burden of malignant tumors with increasing incidence and mortality rates underscores the urgent need for more effective and less toxic therapeutic options. Herbal compounds are being increasingly studied for their potential to meet these needs due to their reduced side
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The growing global burden of malignant tumors with increasing incidence and mortality rates underscores the urgent need for more effective and less toxic therapeutic options. Herbal compounds are being increasingly studied for their potential to meet these needs due to their reduced side effects and significant efficacy. Pristimerin (PS), a triterpenoid from the quinone formamide class derived from the Celastraceae and Hippocrateaceae families, has emerged as a potent anticancer agent. It exhibits broad-spectrum anti-tumor activity across various cancers such as breast, pancreatic, prostate, glioblastoma, colorectal, cervical, and lung cancers. PS modulates several key cellular processes, including apoptosis, autophagy, cell migration and invasion, angiogenesis, and resistance to chemotherapy, targeting crucial signaling pathways such as those involving NF-κB, p53, and STAT3, among others. The main objective of this review is to provide a comprehensive synthesis of the current literature on PS, emphasizing its mechanisms of action and molecular targets with the utmost clarity. It discusses the comparative advantages of PS over current cancer therapies and explores the implications for future research and clinical applications. By delineating the specific pathways and targets affected by PS, this review seeks to offer valuable insights and directions for future research in this field. The information gathered in this review could pave the way for the successful development of PS into a clinically applicable anticancer therapy.
Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Products in Internal Diseases)
Open AccessArticle
Insulin Treatment Does Not Prevent EARLY Autonomic Cardiovascular and Diastolic Dysfunctions in Streptozotocin-Induced Diabetic Rats
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Sarah C. F. Freitas, Marina R. H. Dutra, Paulo M. M. Dourado, Victor Hugo de Martins Miranda, Camila P. dos Santos, Iris C. Sanches, Maria-Cláudia Irigoyen and Kátia De Angelis
Pharmaceuticals 2024, 17(5), 577; https://doi.org/10.3390/ph17050577 - 30 Apr 2024
Abstract
Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced
[...] Read more.
Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk.
Full article
(This article belongs to the Special Issue Cardiovascular Neuromodulatory Therapy)
Open AccessArticle
Chlorin Conjugates in Photodynamic Chemotherapy for Triple-Negative Breast Cancer
by
Meden F. Isaac-Lam
Pharmaceuticals 2024, 17(5), 576; https://doi.org/10.3390/ph17050576 - 30 Apr 2024
Abstract
Breast cancer (BC) is the most common type of cancer in women and the number of new cases in the US is still increasing each year. Triple-negative breast cancer (TNBC), which comprises 15–20% of all breast cancer, is a heterogeneous disease and is
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Breast cancer (BC) is the most common type of cancer in women and the number of new cases in the US is still increasing each year. Triple-negative breast cancer (TNBC), which comprises 15–20% of all breast cancer, is a heterogeneous disease and is considered the most aggressive type of breast cancer due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions for treatments. Traditional chemotherapy is the standard protocol for the treatment of TNBC. Toxicity and multidrug resistance are major drawbacks to chemotherapy. The lack of molecular targets and poor prognosis for TNBC prompts an urgent need to discover novel therapeutic strategies to improve clinical outcomes and quality of life for patients. Photodynamic therapy (PDT) or light treatment is a binary anti-cancer procedure that uses a photosensitizer (PS) that, upon light activation, produces cytotoxic oxygen species, destroying tumor cells. PDT is minimally invasive and can be repeated a few times without accumulating significant toxicity in the surrounding tissues. The primary goal of this study was to investigate in vitro photodynamic chemotherapy as a ternary combination therapy using our synthesized photosensitizers (chlorin–vitamin conjugates and their corresponding indium complexes) co-treated with known chemotherapeutic agents (taxol, doxorubicin, cisplatin, fluorouracil, or methotrexate) in the presence of light and determine the optimum conditions as a pre-clinical study of an enhanced tumoricidal effect against TNBC. Our results indicated that the best combination for an effective chemophotodynamic effect involves a ternary treatment of the indium complex of the chlorin–lipoic acid conjugate (InCLA) co-treated with taxol, which exhibited strong synergism at the nanomolar concentration when combined in the presence of visible light irradiation. Other ternary combinations containing taxol with a synergistic anti-tumor effect against TNBC include chlorin–pantothenic acid (CPA) and chlorin–biotin (CBTN) conjugates. Several other ternary combinations containing InCLA, CBTN, and CPA with either cisplatin, fluorouracil, or methotrexate were identified to generate a synergistic or additive effect. The light dosage remained constant, but the dosages of photosensitizers and chemotherapy drugs were varied to obtain the lowest possible concentration for the desired effect. The synergistic, additive or antagonistic effects of the drug combinations were determined based on the Chou–Talalay method, with InCLA–taxol having the lowest combination index (CI) of 0.25. Fluorescence and transmission electron microscopy (TEM) images provided evidence of apoptosis as the preferred mode of cell death. Our study demonstrated the combination of PDT and chemotherapy as a potential treatment option for TNBC patients.
Full article
(This article belongs to the Special Issue Photodynamic Therapy 2023)
Open AccessArticle
Characterization, Biocompatibility and Antioxidant Activity of Hydrogels Containing Propolis Extract as an Alternative Treatment in Wound Healing
by
Lindalva Maria de Meneses Costa Ferreira, Yuri Yoshioka Modesto, Poliana Dimsan Queiroz de Souza, Fabiana Cristina de Araújo Nascimento, Rayanne Rocha Pereira, Attilio Converti, Desireé Gyles Lynch, Davi do Socorro Barros Brasil, Edilene Oliveira da Silva, José Otávio Carréra Silva-Júnior and Roseane Maria Ribeiro-Costa
Pharmaceuticals 2024, 17(5), 575; https://doi.org/10.3390/ph17050575 - 30 Apr 2024
Abstract
Hydrogels consist of a network of highly porous polymeric chains with the potential for use as a wound dressing. Propolis is a natural product with several biological properties including anti-inflammatory, antibacterial and antioxidant activities. This study was aimed at synthesizing and characterizing a
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Hydrogels consist of a network of highly porous polymeric chains with the potential for use as a wound dressing. Propolis is a natural product with several biological properties including anti-inflammatory, antibacterial and antioxidant activities. This study was aimed at synthesizing and characterizing a polyacrylamide/methylcellulose hydrogel containing propolis as an active ingredient, to serve as a wound dressing alternative, for the treatment of skin lesions. The hydrogels were prepared using free radical polymerization, and were characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetry, differential scanning calorimetry, swelling capacity, mechanical and rheological properties, UV-Vis spectroscopy, antioxidant activity by the DPPH, ABTS and FRAP assays and biocompatibility determined in Vero cells and J774 macrophages by the MTT assay. Hydrogels showed a porous and foliaceous structure with a well-defined network, a good ability to absorb water and aqueous solutions simulating body fluids as well as desirable mechanical properties and pseudoplastic behavior. In hydrogels containing 1.0 and 2.5% propolis, the contents of total polyphenols were 24.74 ± 1.71 mg GAE/g and 32.10 ± 1.01 mg GAE/g and those of total flavonoids 8.01 ± 0.99 mg QE/g and 13.81 ± 0.71 mg QE/g, respectively, in addition to good antioxidant activity determined with all three methods used. Therefore, hydrogels containing propolis extract, may serve as a promising alternative wound dressing for the treatment of skin lesions, due to their anti-oxidant properties, low cost and availability.
Full article
(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications 2024)
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Open AccessReview
Potential Anti-Tumorigenic Properties of Diverse Medicinal Plants against the Majority of Common Types of Cancer
by
Ghosoon Albahri, Adnan Badran, Zaher Abdel Baki, Mohamad Alame, Akram Hijazi, Anis Daou and Elias Baydoun
Pharmaceuticals 2024, 17(5), 574; https://doi.org/10.3390/ph17050574 - 30 Apr 2024
Abstract
Globally, cancer is one of the primary causes of both morbidity and mortality. To prevent cancer from getting worse, more targeted and efficient treatment plans must be developed immediately. Recent research has demonstrated the benefits of natural products for several illnesses, and these
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Globally, cancer is one of the primary causes of both morbidity and mortality. To prevent cancer from getting worse, more targeted and efficient treatment plans must be developed immediately. Recent research has demonstrated the benefits of natural products for several illnesses, and these products have played a significant role in the development of novel treatments whose bioactive components serve as both chemotherapeutic and chemo-preventive agents. Phytochemicals are naturally occurring molecules obtained from plants that have potential applications in both cancer therapy and the development of new medications. These phytochemicals function by regulating the molecular pathways connected to the onset and progression of cancer. Among the specific methods are immune system control, inducing cell cycle arrest and apoptosis, preventing proliferation, raising antioxidant status, and inactivating carcinogens. A thorough literature review was conducted using Google Scholar, PubMed, Scopus, Google Patent, Patent Scope, and US Patent to obtain the data. To provide an overview of the anticancer effects of several medicinal plants, including Annona muricata, Arctium lappa, Arum palaestinum, Cannabis sativa, Catharanthus roseus, Curcuma longa, Glycyrrhiza glabra, Hibiscus, Kalanchoe blossfeldiana, Moringa oleifera, Nerium oleander, Silybum marianum, Taraxacum officinale, Urtica dioica, Withania somnifera L., their availability, classification, active components, pharmacological activities, signaling mechanisms, and potential side effects against the most common cancer types were explored.
Full article
(This article belongs to the Special Issue Plant-Derived Natural Compounds as Bioactive Molecules with Beneficial Effects on Human Health)
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Open AccessArticle
Anti-Biofilm and Anti-Quorum-Sensing Activity of Inula Extracts: A Strategy for Modulating Chromobacterium violaceum Virulence Factors
by
Petya D. Dimitrova, Viktoria Ivanova, Antoaneta Trendafilova and Tsvetelina Paunova-Krasteva
Pharmaceuticals 2024, 17(5), 573; https://doi.org/10.3390/ph17050573 - 30 Apr 2024
Abstract
The formation of microbial biofilm is a self-organizing process among bacterial cells, regulated by quorum-sensing (QS) mechanisms, contributing to development of infections. These processes, either separately or in combination, significantly contribute to bacterial resistance to antibiotics and disinfectants. A novel approach to addressing
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The formation of microbial biofilm is a self-organizing process among bacterial cells, regulated by quorum-sensing (QS) mechanisms, contributing to development of infections. These processes, either separately or in combination, significantly contribute to bacterial resistance to antibiotics and disinfectants. A novel approach to addressing the challenge of treating infections due to antibacterial resistance involves the use of plant metabolites. In recent years, there has been increasing recognition of different phytochemicals as potential modulators. In our study, we evaluated the synergistic effect of chloroform and methanol extracts from Inula species against key virulence factors, including biofilm formation, violacein production, and swarming motility. Each of the 11 examined plant extracts demonstrated the ability to reduce biofilms and pigment synthesis in C. violaceum. Two of the extracts from I. britannica exhibited significant anti-biofilm and anti-quorum-sensing effects with over 80% inhibition. Their inhibitory effect on violacein synthesis indicates their potential as anti-QS agents, likely attributed to their high concentration of terpenoids (triterpenoids, sesquiterpene lactones, and diterpenoids). Scanning electron microscopy revealed a notable reduction in biofilm biomass, along with changes in biofilm architecture and cell morphology. Additionally, fluorescence microscopy revealed the presence of metabolically inactive cells, indicating the potent activity of the extracts during treatment. These new findings underscore the effectiveness of the plant extracts from the genus Inula as potential anti-virulent agents against C. violaceum. They also propose a promising strategy for preventing or treating its biofilm formation.
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(This article belongs to the Special Issue Plant- , Microbial- and Marine-Derived Natural Product Research in Drug Discovery: Strengths and Perspectives)
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Bee Venom-Loaded Niosomes as Innovative Platforms for Cancer Treatment: Development and Therapeutical Efficacy and Safety Evaluation
by
Maria Beatriz Pinto, Patrícia C. Pires, Ricardo C. Calhelha, Ana Rita Silva, Maria João Sousa, Miguel Vilas-Boas, Soraia I. Falcão, Francisco Veiga, Pooyan Makvandi and Ana Cláudia Paiva-Santos
Pharmaceuticals 2024, 17(5), 572; https://doi.org/10.3390/ph17050572 - 29 Apr 2024
Abstract
Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments lacking efficiency and leading to severe side effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have
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Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments lacking efficiency and leading to severe side effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150 nm) and homogeneous (polydispersity index of 0.162) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models (inhibitory concentrations between 12.37 ng/mL and 14.72 ng/mL). Additionally, they also revealed substantial anti-inflammatory activity (inhibitory concentration of 28.98 ng/mL), effects complementary to direct antitumor activity. Niosome safety was also assessed, both in vitro (skin, liver, and kidney cells) and ex vivo (hen’s egg chorioallantoic membrane), and results showed that compound encapsulation increased its safety. Hence, small, and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies. Future research should focus on evaluating the potential of the developed platform in in vivo models.
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(This article belongs to the Special Issue Pharmacological Properties and Therapeutic Potential of Honey Bee Products)
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The Therapeutic Potential of Essential Oils in Managing Inflammatory Skin Conditions: A Scoping Review
by
Anouk E. W. K. Dontje, Catharina C. M. Schuiling-Veninga, Florence P. A. M. van Hunsel, Corine Ekhart, Fatih Demirci and Herman J. Woerdenbag
Pharmaceuticals 2024, 17(5), 571; https://doi.org/10.3390/ph17050571 - 29 Apr 2024
Abstract
Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils
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Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils (EOs). This scoping review aims to generate a broad overview of the EOs used to treat inflammatory skin conditions, namely, acne vulgaris, dermatitis and eczema, psoriasis, and rosacea, in a clinical setting. The quality, efficacy, and safety of various EOs, as well as the way in which they are prepared, are reviewed, and the potential, as well as the limitations, of EOs for the treatment of inflammatory skin conditions are discussed. Twenty-nine eligible studies (case studies, uncontrolled clinical studies, and randomized clinical studies) on the applications of EOs for inflammatory skin conditions were retrieved from scientific electronic databases (PubMed, Embase, Scopus, and the Cochrane Library). As an initial result, tea tree (Melaleuca alternifolia) oil emerged as the most studied EO. The clinical studies with tea tree oil gel for acne treatment showed an efficacy with fewer adverse reactions compared to conventional treatments. The uncontrolled studies indicated the potential efficacy of ajwain (Trachyspermum ammi) oil, eucalyptus (Eucalyptus globulus) oil, and cedarwood (Cedrus libani) oil in the treatment of acne, but further research is required to reach conclusive evidence. The placebo-controlled studies revealed the positive effects of kānuka (Kunzea ericoides) oil and frankincense (Boswellia spp.) oil in the treatment of psoriasis and eczema. The quality verification of the EO products was inconsistent, with some studies lacking analyses and transparency. The quality limitations of some studies included a small sample size, a short duration, and the absence of a control group. This present review underscores the need for extended, well-designed clinical studies to further assess the efficacy and safety of EOs for treating inflammatory skin conditions with products of assured quality and to further elucidate the mechanisms of action involved.
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(This article belongs to the Special Issue Multi-Targeted Natural Products as Therapeutics)
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Synthesis and Evaluation of 5-(Heteroarylmethylene)hydantoins as Glycogen Synthase Kinase-3β Inhibitors
by
Nicholas O. Schneider, Kendra Gilreath, Daniel J. Burkett, Martin St. Maurice and William A. Donaldson
Pharmaceuticals 2024, 17(5), 570; https://doi.org/10.3390/ph17050570 - 29 Apr 2024
Abstract
Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule
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Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory activities including for GSK-3β. A family of fourteen 2-heterocycle substituted methylene hydantoins (14, 17–29) were prepared and evaluated for the inhibition of GSK-3β at 25 μM. The IC50 values of five of these compounds was determined; the two best inhibitors are 5-[(4′-chloro-2-pyridinyl)methylene]hydantoin (IC50 = 2.14 ± 0.18 μM) and 5-[(6′-bromo-2-pyridinyl)methylene]hydantoin (IC50 = 3.39 ± 0.16 μM). The computational docking of the compounds with GSK-3β (pdb 1q41) revealed poses with hydrogen bonding to the backbone at Val135. The 5-[(heteroaryl)methylene]hydantoins did not strongly inhibit other metalloenzymes, demonstrating poor inhibitory activity against matrix metalloproteinase-12 at 25 μM and against human carbonic anhydrase at 200 μM, and were not inhibitors for Staphylococcus aureus pyruvate carboxylase at concentrations >1000 μM.
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(This article belongs to the Special Issue Nitrogen Containing Scaffolds in Medicinal Chemistry 2023)
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Computational Modeling to Identify Drugs Targeting Metastatic Castration-Resistant Prostate Cancer Characterized by Heightened Glycolysis
by
Mei-Chi Su, Adam M. Lee, Weijie Zhang, Danielle Maeser, Robert F. Gruener, Yibin Deng and R. Stephanie Huang
Pharmaceuticals 2024, 17(5), 569; https://doi.org/10.3390/ph17050569 - 29 Apr 2024
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) remains a deadly disease due to a lack of efficacious treatments. The reprogramming of cancer metabolism toward elevated glycolysis is a hallmark of mCRPC. Our goal is to identify therapeutics specifically associated with high glycolysis. Here, we established
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Metastatic castration-resistant prostate cancer (mCRPC) remains a deadly disease due to a lack of efficacious treatments. The reprogramming of cancer metabolism toward elevated glycolysis is a hallmark of mCRPC. Our goal is to identify therapeutics specifically associated with high glycolysis. Here, we established a computational framework to identify new pharmacological agents for mCRPC with heightened glycolysis activity under a tumor microenvironment, followed by in vitro validation. First, using our established computational tool, OncoPredict, we imputed the likelihood of drug responses to approximately 1900 agents in each mCRPC tumor from two large clinical patient cohorts. We selected drugs with predicted sensitivity highly correlated with glycolysis scores. In total, 77 drugs predicted to be more sensitive in high glycolysis mCRPC tumors were identified. These drugs represent diverse mechanisms of action. Three of the candidates, ivermectin, CNF2024, and P276-00, were selected for subsequent vitro validation based on the highest measured drug responses associated with glycolysis/OXPHOS in pan-cancer cell lines. By decreasing the input glucose level in culture media to mimic the mCRPC tumor microenvironments, we induced a high-glycolysis condition in PC3 cells and validated the projected higher sensitivity of all three drugs under this condition (p < 0.0001 for all drugs). For biomarker discovery, ivermectin and P276-00 were predicted to be more sensitive to mCRPC tumors with low androgen receptor activities and high glycolysis activities (AR(low)Gly(high)). In addition, we integrated a protein–protein interaction network and topological methods to identify biomarkers for these drug candidates. EEF1B2 and CCNA2 were identified as key biomarkers for ivermectin and CNF2024, respectively, through multiple independent biomarker nomination pipelines. In conclusion, this study offers new efficacious therapeutics beyond traditional androgen-deprivation therapies by precisely targeting mCRPC with high glycolysis.
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(This article belongs to the Special Issue Novel Therapies for the Treatment of Metastatic Prostate Cancer)
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Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease—A Narrative Clinical Review
by
Nikolaos Velidakis, Panagiotis Stachteas, Evangelia Gkougkoudi, Christodoulos Papadopoulos and Nikolaos P. E. Kadoglou
Pharmaceuticals 2024, 17(5), 568; https://doi.org/10.3390/ph17050568 - 29 Apr 2024
Abstract
Diabetic atherosclerosis is a complex process that is characterized by diffuse and unstable lesions increasing 2–4-fold the risk of adverse cardiovascular (CV) events. Diabetic dyslipidemia has a predominant role in coronary artery disease (CAD) and has been the target of classical and emerging
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Diabetic atherosclerosis is a complex process that is characterized by diffuse and unstable lesions increasing 2–4-fold the risk of adverse cardiovascular (CV) events. Diabetic dyslipidemia has a predominant role in coronary artery disease (CAD) and has been the target of classical and emerging pharmaceutical agents with established or promising CV benefits. The aim of the present narrative review was to summarize the effects of classical and novel lipid-lowering pharmaceutical agents on lipid profile and CV outcomes in diabetic patients with established CAD or high risk of CAD. Statins remain the first-line treatment for all diabetic patients since they considerably ameliorate lipid parameters and non-lipid CV risk factors, leading to reduced CV morbidity and mortality. Complementary to statins, ezetimibe exerts lipid-lowering properties with modest but significant reductions in major adverse cardiovascular events (MACEs) and CV mortality. PCSK9 inhibitors considerably reduce LDL-C levels and lower MACEs in diabetic patients. On the other hand, fibrates may confer a very modest decline in MACE incidence, while the CV impact of omega-3 fatty acids is promising but remains questionable. Bempedoic acid and inclisiran have a potential therapeutic role in the management of diabetic dyslipidemia, but this is still not adequately documented. Given the heightened CV risk among individuals with diabetes, more decisive results would be of great importance in the utility of all these drugs.
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(This article belongs to the Section Pharmacology)
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Persistence in the Methadone Maintenance Program and Its Relationship with the Medication Regimen Complexity Index in Opioid-Dependent Patients
by
Elena Alba Álvaro-Alonso, María del Carmen Gómez-Álvarez, Beatriz Segovia-Tapiador, María Isabel Del-Pino-Illaconza, Jorge Valencia, Pablo Ryan, Antonio Aguilar-Ros and Ismael Escobar-Rodríguez
Pharmaceuticals 2024, 17(5), 567; https://doi.org/10.3390/ph17050567 - 29 Apr 2024
Abstract
It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has
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It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has not been studied. The aim of this study is to calculate the Methadone Maintenance Program (MMP) persistence and the MRCI score in a ODP cohort. Second, to analyze its relationship and association with other variables. To accomplish this research, an observational study including adults with a confirmed diagnosis of opiate-dependency according to the DSM-5 in a MMP center was carried out. To define MMP-persistence, a group was created by the researchers who defined five weighted items according to their agreed importance. Our first contribution was to create a new definition of MMP-persistence. This study also identified age, comorbidities, and received methadone maintenance doses as successful predictors for MMP-persistence. We have also shown that the MRCI does not seem to be a useful tool to determine MMP-persistence, probably because there are multiple factors that influence it in addition to the CPR. It is necessary to continue searching for more precise selection and stratification tools for ODP to improve their persistence.
Full article
(This article belongs to the Special Issue Drug Safety and Relevant Issues in the Real-World 2024)
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