Next Issue
Volume 18, January
Previous Issue
Volume 17, November
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.1
4.3
Journals
Pharmaceuticals
Volume 17
Issue 12
share announcement

Pharmaceuticals, Volume 17, Issue 12 (December 2024) – 183 articles

Cover Story (view full-size image): Molecular imaging is a growing field, driven by technological advances such as the improvement in PET-CT scanners, which has resulted in much higher sensitivity and a variety of new radiopharmaceuticals that allow for the visualization of specific molecular pathways and even theragnostic approaches. In oncology, the development of dedicated tracers is crucial for personalized therapeutic approaches. Novel peptides allow for the visualization of many different targets such as PD-1 and PD-L1 expression, chemokine expression, HER expression, T-cell imaging, microenvironmental imaging such as FAP imaging, and many others. In this article, we review recent advances in the development of non-[18F]FDG PET radiopharmaceuticals and their current clinical applications in oncology as well as some future aspects. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
40 pages, 15661 KiB  
Review
Breath and Beyond: Advances in Nanomedicine for Oral and Intranasal Aerosol Drug Delivery
by Simeng Du, Zhiyang Wen, Jinghan Yu, Yingying Meng, Yuling Liu and Xuejun Xia
Pharmaceuticals 2024, 17(12), 1742; https://doi.org/10.3390/ph17121742 - 23 Dec 2024
Viewed by 872
Abstract
Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for [...] Read more.
Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for treating respiratory diseases worldwide. With advancements in disease understanding and the development of aerosolized nano drug delivery systems, the application of OIADD has exceeded its traditional boundaries, demonstrating significant potential in the treatment of non-respiratory conditions as well. This study provides a comprehensive overview of the applications of oral and intranasal aerosol formulations in disease treatment. It examines the key challenges limiting the development of nanomedicines in drug delivery systems, formulation processes, and aerosol devices and explores the latest advancements in these areas. This review aims to offer valuable insights to researchers involved in the development of aerosol delivery platforms. Full article
(This article belongs to the Section Pharmaceutical Technology)
►▼ Show Figures

Graphical abstract

34 pages, 7313 KiB  
Review
Sodium Thiosulfate: An Innovative Multi-Target Repurposed Treatment Strategy for Late-Onset Alzheimer’s Disease
by Melvin R. Hayden and Neetu Tyagi
Pharmaceuticals 2024, 17(12), 1741; https://doi.org/10.3390/ph17121741 - 23 Dec 2024
Viewed by 784
Abstract
Late-onset Alzheimer’s disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of [...] Read more.
Late-onset Alzheimer’s disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood–brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood–cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies for Alzheimer’s Disease Treatment)
►▼ Show Figures

Graphical abstract

11 pages, 2557 KiB  
Article
Effects of Hispidulin on the Osteo/Odontogenic and Endothelial Differentiation of Dental Pulp Stem Cells
by Yeon Kim, Hyun-Joo Park, Mi-Kyoung Kim, Hyung Joon Kim, Yong-Il Kim, Soo-Kyung Bae and Moon-Kyoung Bae
Pharmaceuticals 2024, 17(12), 1740; https://doi.org/10.3390/ph17121740 - 23 Dec 2024
Viewed by 488
Abstract
Background: Human dental pulp stem cells (HDPSCs) with multi-lineage differentiation potential and migration ability are required for HDPSC-based bone and dental regeneration. Hispidulin is a naturally occurring flavonoid with diverse pharmacological activities, but its effects on biological properties of HDPSCs remain unknown. Therefore, [...] Read more.
Background: Human dental pulp stem cells (HDPSCs) with multi-lineage differentiation potential and migration ability are required for HDPSC-based bone and dental regeneration. Hispidulin is a naturally occurring flavonoid with diverse pharmacological activities, but its effects on biological properties of HDPSCs remain unknown. Therefore, we investigated the effects of hispidulin on the differentiation potential and migration ability of HDPSCs and elucidated their underlying mechanisms. Methods: The osteo/odontogenic capacity of HDPSCs was assessed using the alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. The migration ability of HDPSCs was evaluated using a scratch wound assay. Furthermore, the endothelial differentiation of HDPSCs was examined by using a capillary sprouting assay and by assessing CD31 expression. Results: Hispidulin significantly enhanced the osteo/odontogenic differentiation of HDPSCs with increased expression of osteo/odontogenic differentiation markers. Hispidulin increased the migration of HDPSCs, which was mediated by the upregulation of C-X-C chemokine receptor type 4 (CXCR4). The treatment of HDPSCs with hispidulin enhanced the differentiation of HDPSCs into endothelial cells, as evidenced by increased capillary sprouting and endothelial marker expression. In addition, we demonstrated that hispidulin activated the ERK1/2 signaling, and its inhibition by U0126 significantly suppressed the hispidulin-induced endothelial differentiation of HDPSCs. Conclusions: These findings demonstrate that hispidulin effectively promotes the osteo/odontogenic and endothelial differentiation, and migration of HDPSCs. These results suggest that hispidulin may have potential therapeutic applications in dental pulp regeneration and tissue engineering. Full article
(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues 2024)
►▼ Show Figures

Graphical abstract

18 pages, 6175 KiB  
Article
Safety Evaluation of the Combination with Dexrazoxane and Anthracyclines: A Disproportionality Analysis Based on the Food and Drug Administration Adverse Event Reporting System Database
by Danyi Liu, Junting Liu, Rui Xiao, Anqi Deng and Wei Liu
Pharmaceuticals 2024, 17(12), 1739; https://doi.org/10.3390/ph17121739 - 23 Dec 2024
Viewed by 731
Abstract
Objectives: As one of the important interventions to alleviate anthracycline-related cardiotoxicity (ARC), the safety assessment of dexrazoxane in clinical practice is particularly important. This study aims to evaluate the actual efficacy and potential adverse effects of dexrazoxane in clinical practice by analyzing [...] Read more.
Objectives: As one of the important interventions to alleviate anthracycline-related cardiotoxicity (ARC), the safety assessment of dexrazoxane in clinical practice is particularly important. This study aims to evaluate the actual efficacy and potential adverse effects of dexrazoxane in clinical practice by analyzing the reports of adverse events (AEs) related to the combination with dexrazoxane and anthracyclines. Methods: We utilized four disproportionality analysis methods to analyze AE reports of the combination with dexrazoxane and anthracyclines in the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2014 to the first quarter of 2024. Results: Under the three backgrounds, a large number of preferred terms (PTs) such as cardiac failure disappeared in the combined group, and the PTs with significant signal values were mainly concentrated in infections and infestations. For patients under 18, some PTs associated with infections and infestations disappeared after the combination of the two drugs. Conclusions: Dexrazoxane can effectively alleviate ARC, but it may also increase the risk of infection. For infections and infestations, children under 18 years old are more likely to benefit from the combination therapy. More attention should be paid to infectious AEs in the clinical use of dexrazoxane, though disproportionality analysis is a hypothesis-generating approach. Full article
►▼ Show Figures

Figure 1

22 pages, 2661 KiB  
Review
The Role of Antioxidant Plant Extracts’ Composition and Encapsulation in Dietary Supplements and Gemmo-Derivatives, as Safe Adjuvants in Metabolic and Age-Related Conditions: A Review
by Bogdan-Stefan Negreanu-Pirjol, Ticuta Negreanu-Pirjol, Florica Busuricu, Sanda Jurja, Oana Craciunescu, Ovidiu Oprea, Ludmila Motelica, Elena Iulia Oprita and Florentina Nicoleta Roncea
Pharmaceuticals 2024, 17(12), 1738; https://doi.org/10.3390/ph17121738 - 23 Dec 2024
Viewed by 987
Abstract
Given the current global circumstances, marked by severe environmental pollution—including the contamination of food—along with daily stress and a sedentary lifestyle, many consumers choose to improve their quality of life by using, among others, minimally processed food, food supplements, and gemmo-derivatives. Recent lab [...] Read more.
Given the current global circumstances, marked by severe environmental pollution—including the contamination of food—along with daily stress and a sedentary lifestyle, many consumers choose to improve their quality of life by using, among others, minimally processed food, food supplements, and gemmo-derivatives. Recent lab and clinical studies have shown the positive impact of specific nutrients with antioxidant capacities in the treatment of several conditions generated by oxidative stress. This paper reviews antioxidant plant extracts utilized as components in various dietary supplements and gemmoderivatives, highlighting their chemical composition and biological properties in preventing diseases caused by oxidative stress. A modern approach to food science brings to the fore the concept of dietary supplements vs. functional food, nutraceuticals, and gemmo-derivatives. The definitions of these terms are not being unanimously regulated in this respect and describe each category of compound and product, also emphasizing the need to implement adequate nutrivigilance. In order to enhance the absorption and bioavailability of dietary supplements and gemmo-derivatives based on antioxidant plant extracts, some encapsulation techniques are outlined. Full article
(This article belongs to the Section Natural Products)
►▼ Show Figures

Figure 1

18 pages, 5994 KiB  
Article
Study of the Effect of Temperature on the Production of Carrageenan-Based Buccal Films and Optimization of the Process Parameters
by Katalin Kristó, Anahita Sangestani, Alharith A. A. Hassan, Hala Rayya, Krisztián Pamlényi, András Kelemen and Ildikó Csóka
Pharmaceuticals 2024, 17(12), 1737; https://doi.org/10.3390/ph17121737 - 22 Dec 2024
Viewed by 736
Abstract
Background/Objectives: Films in the mouth offer a promising alternative drug delivery system for oral administration, with several advantages over traditional oral formulations. Furthermore, their non-invasive nature and easy administration make them conducive to increasing patient compliance. The use of active agents in these [...] Read more.
Background/Objectives: Films in the mouth offer a promising alternative drug delivery system for oral administration, with several advantages over traditional oral formulations. Furthermore, their non-invasive nature and easy administration make them conducive to increasing patient compliance. The use of active agents in these films can further improve their drug delivery properties, making them an even more useful drug delivery system. Methods: In this research, carrageenan was used as a polymer, while glycerine was added as a plasticizer, furthermore, lidocaine hydrochloride and diclofenac sodium were used as the active agents. The prepared films were characterized by analytical techniques. Results: The results showed that glycerine reduced the mucoadhesivity and breaking hardness of the films and increasing the temperature made the films brittle. These results are also confirmed by the statistical analysis. Based on the FTIR results, glycerine can be used in films without structural changes. Conclusions: Based on the findings, films prepared from a solution with a concentration of 1.5% carrageenan and 1.5% glycerine at 70 °C are suitable as a drug delivery system for use on the buccal mucosa when combined with active agents. Carrageenan was successfully used as a carrier for two different types of active agents. Full article
(This article belongs to the Special Issue Pharmaceutical Formulation Characterization Design)
►▼ Show Figures

Figure 1

14 pages, 3079 KiB  
Article
Integrated Network-Based Analysis of Diseases Associated with Amyloid Deposition Through a Disease–Protein–Drug Network
by Aikaterini E. I. Rizou, Georgia I. Nasi, Avgi E. Apostolakou, Meletios A. Dimopoulos, Efstathios Kastritis and Vassiliki A. Iconomidou
Pharmaceuticals 2024, 17(12), 1736; https://doi.org/10.3390/ph17121736 - 22 Dec 2024
Viewed by 543
Abstract
Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because [...] Read more.
Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. Methods: For this reason, we constructed a disease–protein–drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition. Apart from the amyloidogenic proteins that self-assemble into fibrils, we also included other co-deposited proteins found in amyloid deposits. Results: In this work, protein–protein, protein–drug, and disease–drug associations were collected to create a heterogenous network. Through disease-based and drug-based analyses, we highlighted commonalities between diseases and proposed an approved drug with prospects of repurposing. Conclusions: The identified disease associations and drug candidates are proposed for further study that will potentially help treat diseases associated with amyloid deposition. Full article
(This article belongs to the Section Biopharmaceuticals)
►▼ Show Figures

Graphical abstract

18 pages, 5649 KiB  
Review
The Significant Therapeutic Effects of Chinese Scorpion: Modern Scientific Exploration of Ion Channels
by Yueyuan Zheng, Qiuyi Wen, Yushi Huang and Dean Guo
Pharmaceuticals 2024, 17(12), 1735; https://doi.org/10.3390/ph17121735 - 22 Dec 2024
Viewed by 618
Abstract
Chinese scorpion (CS), a traditional animal-based medicine used for over a millennium, has been documented since AD 935–960. It is derived from the scorpion Buthus martensii Karsch and is used to treat various ailments such as stroke, epilepsy, rheumatism, and more. Modern research [...] Read more.
Chinese scorpion (CS), a traditional animal-based medicine used for over a millennium, has been documented since AD 935–960. It is derived from the scorpion Buthus martensii Karsch and is used to treat various ailments such as stroke, epilepsy, rheumatism, and more. Modern research has identified the pharmacological mechanisms behind its traditional uses, with active components like venom and proteins showing analgesic, antitumor, antiepileptic, and antithrombotic effects. Studies reveal that CS affects ion channels, crucial for cellular functions, through interactions with sodium, potassium, and calcium channels, potentially explaining its therapeutic effects. Future research aims to elucidate the precise mechanisms, target specific ion channel subtypes, and validate clinical efficacy and safety, paving the way for novel therapies based on these natural compounds. Full article
(This article belongs to the Section Natural Products)
►▼ Show Figures

Figure 1

15 pages, 1366 KiB  
Article
Effect of Homologous and Heterologous Booster in COVID-19 Vaccination
by Marija Vukčević, Mateja Despot, Aleksandra Nikolić-Kokić, Duško Blagojević, Milan Nikolić, Ana Banko, Tanja Jovanović and Dragana Despot
Pharmaceuticals 2024, 17(12), 1734; https://doi.org/10.3390/ph17121734 - 22 Dec 2024
Viewed by 761
Abstract
Background: COVID-19 became a global health crisis in early 2020, and the way out of the crisis was the rapid development of vaccines by Sinopharm, Pfizer, and Sputnik, among others, which played a crucial role in controlling the pandemic. Therefore, this study aims [...] Read more.
Background: COVID-19 became a global health crisis in early 2020, and the way out of the crisis was the rapid development of vaccines by Sinopharm, Pfizer, and Sputnik, among others, which played a crucial role in controlling the pandemic. Therefore, this study aims to investigate the long-term immune response by measuring the levels of anti-S1 IgG antibodies induced by homologous and heterologous vaccination regimens. Methods: We investigated the titer of the anti-S1 IgG antibody produced for the viral surface antigen 3, 6 months after the second dose, before the third dose, and 1, 3, and 6 months after the third dose. Results: Anti-S1 IgG antibody levels significantly increased three/six months after the second dose and following the booster in individuals without prior COVID-19 infection who received all three homologous vaccine doses. The group that initially responded poorly to Sinopharm showed a significant and sustained increase after receiving the Pfizer booster. Additionally, prior SARS-CoV-2 infection between primary and booster vaccination boosted anti-S1 antibody titers in all individuals, regardless of the vaccine used. The highest vaccine efficacy was observed during the primary vaccination period and declined over time, especially during the omicron-dominant period. Conclusions: The results suggest that while homologous and heterologous booster doses can significantly enhance anti-S1 IgG antibody levels, prior SARS-CoV-2 infection and the type of vaccine administered influence the duration and magnitude of the immune response. Full article
(This article belongs to the Section Pharmacology)
►▼ Show Figures

Figure 1

19 pages, 3607 KiB  
Article
Mass Spectrometric Based Metabolomics of the Saudi Cultivar of Fenugreek (Trigonella foenum-graecum L.): A Combined GC-MS, Antimicrobial and Computational Approach
by Nujud A. M. Almuzaini, Abdel Moneim E. Sulieman, Naimah A. Alanazi, Riadh Badraoui and Emad M. Abdallah
Pharmaceuticals 2024, 17(12), 1733; https://doi.org/10.3390/ph17121733 - 21 Dec 2024
Viewed by 997
Abstract
Background and Objective: In Saudi Arabia, numerous plant species with promising medicinal properties are cultivated, widely traded, and commonly utilized in traditional medicine, including fenugreek (Trigonella foenum-graecum). This study aimed to comprehensively assess the phytochemical composition and antimicrobial potential of the [...] Read more.
Background and Objective: In Saudi Arabia, numerous plant species with promising medicinal properties are cultivated, widely traded, and commonly utilized in traditional medicine, including fenugreek (Trigonella foenum-graecum). This study aimed to comprehensively assess the phytochemical composition and antimicrobial potential of the Saudi cultivar of fenugreek using an integrative approach combining in vitro and in silico methodologies. Methods: A comprehensive investigation was conducted on the ethanol extract of fenugreek seeds, assessing its antibacterial, antifungal, properties. Computational modeling was employed to predict pharmacokinetic behavior and potential toxicity of the identified bioactive compounds. Results: Qalitative phytochemical analysis showed presence of alkaloids, tannins, saponins, glycosides, flavonoids, and steroids, while terpenoids were notably absent. GC-MS analysis of Trigonella foenum-graecum (fenugreek) seeds identified 25 bioactive compounds, with Ethyl methane sulfonate (12.41%) being the predominant component. Other key compounds included n-Hexadecanoic acid, 4-Butyl-2(4-nitrophenyl)-1,3-thiazole, and α-Tocopherol. In silico modeling of fenugreek phytochemicals supported their antibacterial, antioxidant, and neuroprotective potential, with compounds 21 and 24 showing strong binding to key targets like Tyrosyl-tRNA Synthetase (TyrRS) of Staphylococcus aureus (S. aureus), Aspartic proteinase from Candida albicans (C. albicans) and human peroxiredoxin 5. Pharmacokinetic analysis indicated good oral bioavailability, minimal CYP inhibition, and blood-brain barrier penetration, suggesting potential for treating neurodegenerative diseases. These bioactive compounds, including diosgenin and trigonelline, support fenugreek’s therapeutic promise and warrant further in vitro, in vivo, and clinical studies. Conclusion: The Saudi fenugreek cultivar is rich in bioactive compounds with good antibacterial potential. These findings establish a robust foundation for continued pharmacological research on the Saudi cultivar of T. foenum-graecum, highlighting its potential as a rich source of bioactive compounds with significant medicinal value. Full article
►▼ Show Figures

Graphical abstract

14 pages, 6584 KiB  
Article
The Role of Curcumin in Preventing Naturally Occurring Leiomyoma in the Galline Model
by Kazim Sahin, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Ibrahim H. Ozercan, Nashwa Kabil, Omer Kucuk and Bulent Ozpolat
Pharmaceuticals 2024, 17(12), 1732; https://doi.org/10.3390/ph17121732 - 21 Dec 2024
Viewed by 809
Abstract
Background: Leiomyoma (LM) is the most commonly identified tumor in the genital tract, occurring in 70–80% of women. The only treatment option is surgery, which significantly influences healthcare costs and negatively influences women’s survival and reproductive capacity. Therefore, identifying safe and effective chemopreventive [...] Read more.
Background: Leiomyoma (LM) is the most commonly identified tumor in the genital tract, occurring in 70–80% of women. The only treatment option is surgery, which significantly influences healthcare costs and negatively influences women’s survival and reproductive capacity. Therefore, identifying safe and effective chemopreventive and treatment modalities is needed. Methods: We investigated the effects of 12 months of daily curcumin (0, 25.8, and 53 mg/kg) diet on the incidence and growth of spontaneously developing LM tumors in a galline (hen) model. Results: LM tumors were detected in 58.9% (53/90) of the control hens as spontaneous occurrences, while they were observed in 37.7% (34/90) and 24.5% (22/90) of hens treated with daily doses of 25.8 mg or 53.0 mg, respectively, over 12 months. This reduced LM development by 35% and 58.5%, respectively (p = 0.004). We also observed a dose-dependent inhibition of LM-tumor growth and NF-κB, mTOR, p70S6K1, and 4E-BP1 signaling while inducing Nrf2/HO1 pathway induction LM tumors collected from hens fed with curcumin (p < 0.05). Curcumin intake notably reduced levels of TGF-β1, α-SMA, and collagen type 1, with dose-dependent effects (p < 0.001). Conclusions: The findings suggest that daily curcumin consumption significantly reduces the incidence of naturally occurring LMs and suppresses tumor growth. This indicates that regular curcumin intake may be an effective preventive measure against LMs. Full article
(This article belongs to the Special Issue Natural Compounds as Potential Anticancer, Anti-inflammatory and Antioxidant Agents in Medicine)
►▼ Show Figures

Graphical abstract

16 pages, 6187 KiB  
Article
Aerosol Inhalation of Luteolin-7-O-Glucuronide Exerts Anti-Inflammatory Effects by Inhibiting NLRP3 Inflammasome Activation
by Jianliang Li, Ling Song, Han Li, Yunhang Gao, Tengfei Chen, Zhongxiu Zhang, Hongping Hon, Zuguang Ye and Guangping Zhang
Pharmaceuticals 2024, 17(12), 1731; https://doi.org/10.3390/ph17121731 - 21 Dec 2024
Viewed by 586
Abstract
Background: Luteolin-7-O-glucuronide (L7Gn) is a flavonoid isolated from numerous traditional Chinese herbal medicines that exerts anti-inflammatory effects. Previous research has revealed that aerosol inhalation is the most straightforward way of administration for the delivery of respiratory agents. Thus far, the impact of aerosol [...] Read more.
Background: Luteolin-7-O-glucuronide (L7Gn) is a flavonoid isolated from numerous traditional Chinese herbal medicines that exerts anti-inflammatory effects. Previous research has revealed that aerosol inhalation is the most straightforward way of administration for the delivery of respiratory agents. Thus far, the impact of aerosol inhalation of L7Gn on lung inflammation and the underlying mechanisms remain unknown. Methods: The real-time particle size for L7Gn aerosol inhalation was detected by the Spraytec spray droplet size measurement system, including transmission and size diameters. The acute lung injury (ALI) rat model was induced by aerosol inhalation of LPS to evaluate the protective effect of L7Gn. The inhibitory effect of NLRP3 inflammasome activation assays was conducted in LPS-induced MH-S cells. Elisa, Western blotting, and RT-PCR were utilized to investigate the expression of NLRP3 inflammasome-relevant proteins and genes. Results: In this study, we found that inhalation of L7Gn aerosol significantly reduced pulmonary injury by inhibiting inflammatory infiltration and enhancing lung function. Meanwhile, the NLR family pyrin domain containing 3 (NLRP3) inflammasome was activated dramatically, accompanied by upregulated expression of IL-1β and IL-18, both in the ALI rat model and in LPS-induced MH-S cells. Moreover, L7Gn was found to significantly downregulate the expression of NLRP3, ASC, caspase-1, and cleaved caspase-1, which are critical components of the NLRP3 inflammasome, as well as the expression of IL-1β and IL-18. Conclusions: Based on our findings, L7Gn could exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation, which may emerge as potential therapeutic agents for the treatment of ALI. Full article
(This article belongs to the Section Pharmacology)
►▼ Show Figures

Figure 1

19 pages, 6147 KiB  
Article
Vitamin E Improves Cellular and Structural Bone Histomorphometry in an Alcohol-Induced Osteoporosis Rat Model
by Norazlina Mohamed, Seham Salem Ahmed Abukhadir, Syed Alhafiz Syed Hashim, Nur Sabariah Adnan, Muhamad Arizi Aziz and Norliza Muhammad
Pharmaceuticals 2024, 17(12), 1730; https://doi.org/10.3390/ph17121730 - 20 Dec 2024
Viewed by 679
Abstract
Background: Alcohol-induced osteoporosis is a significant health concern, impairing bone formation and enhancing resorption, thereby weakening skeletal integrity. This study examines the effects of palm vitamin E on bone histomorphometry in a male rat model of alcohol-induced osteoporosis. Methods: Three-month-old Sprague–Dawley [...] Read more.
Background: Alcohol-induced osteoporosis is a significant health concern, impairing bone formation and enhancing resorption, thereby weakening skeletal integrity. This study examines the effects of palm vitamin E on bone histomorphometry in a male rat model of alcohol-induced osteoporosis. Methods: Three-month-old Sprague–Dawley rats were randomized into seven groups, with one baseline control group (BC) and six experimental groups undergoing a two-phase treatment. In the first month, the control group received normal saline, while experimental groups received intraperitoneal alcohol (3 g/kg) three times weekly. For the subsequent two months, alcohol treatment continued in one group (A), while others received olive oil (C), saline (AN), alpha-tocopherol (AA), or palm vitamin E (AE) orally. Results: Femur histomorphometric analysis post-sacrifice showed that alcohol exposure significantly decreased osteoblastic activity and impaired bone microarchitecture, evidenced by reduced Ob.S/BS, OS/BS, OV/BV, Tb.Th, BV/TV, and Tb.N, alongside increased Oc.S/BS, ES/BS, and Tb.Sp. Both alpha-tocopherol and palm vitamin E improved bone parameters, with palm vitamin E showing superior efficacy except in OV/BV. Conclusions: These findings suggest that palm vitamin E may offer a therapeutic benefit for mitigating alcohol-induced bone damage. Full article
(This article belongs to the Special Issue The Pharmacological Management of Bone and Muscle Disorders)
►▼ Show Figures

Figure 1

21 pages, 7602 KiB  
Article
Pentagalloyl Glucose from Bouea macrophylla Suppresses the Epithelial–Mesenchymal Transition and Synergizes the Doxorubicin-Induced Anticancer and Anti-Migration Effects in Triple-Negative Breast Cancer
by Jiraporn Kantapan, Phattarawadee Innuan, Sarawut Kongkarnka, Padchanee Sangthong and Nathupakorn Dechsupa
Pharmaceuticals 2024, 17(12), 1729; https://doi.org/10.3390/ph17121729 - 20 Dec 2024
Viewed by 752
Abstract
Background: Triple-negative breast cancer (TNBC) represents an aggressive form of breast cancer with few available therapeutic options. Chemotherapy, particularly with drugs like doxorubicin (DOX), remains the cornerstone of treatment for this challenging subtype. However, the clinical utility of DOX is hampered by adverse [...] Read more.
Background: Triple-negative breast cancer (TNBC) represents an aggressive form of breast cancer with few available therapeutic options. Chemotherapy, particularly with drugs like doxorubicin (DOX), remains the cornerstone of treatment for this challenging subtype. However, the clinical utility of DOX is hampered by adverse effects that escalate with higher doses and drug resistance, underscoring the need for alternative therapies. This study explored the efficacy of pentagalloyl glucose (PGG), a natural polyphenol derived from Bouea macrophylla, in enhancing DOX’s anticancer effects and suppressing the epithelial–mesenchymal transition (EMT) in TNBC cells. Methods: This study employed diverse methodologies to assess the effects of PGG and DOX on TNBC cells. MDA-MB231 triple-negative breast cancer cells were used to evaluate cell viability, migration, invasion, apoptosis, mitochondrial membrane potential, and protein expression through techniques including MTT assays, wound healing assays, flow cytometry, Western blotting, and immunofluorescence. Results: Our findings demonstrate that PGG combined with DOX significantly inhibits TNBC cell proliferation, migration, and invasion. PGG enhances DOX-induced apoptosis by disrupting the mitochondrial membrane potential and activating caspase pathways; consequently, the activation of caspase-3 and the cleavage of PARP are increased. Additionally, the study shows that the combination treatment upregulates ERK signaling, further promoting apoptosis. Moreover, PGG reverses DOX-induced EMT by downregulating mesenchymal markers (vimentin and β-catenin) and upregulating epithelial markers (E-cadherin). Furthermore, it effectively inhibits STAT3 phosphorylation, associated with cell survival and migration. Conclusions: These results highlight the potential of PGG as an adjuvant therapy in TNBC treatment. PGG synergizes with DOX, which potentiates its anticancer effects while mitigating adverse reactions. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment)
►▼ Show Figures

Graphical abstract

14 pages, 1162 KiB  
Article
Application of LC-MS/MS for the Identification of Drugs of Abuse in Driver’s License Regranting Procedures
by Roberta Tittarelli, Lucrezia Stefani, Leonardo Romani, Federico Mineo, Francesca Vernich, Giulio Mannocchi, Maria Rosaria Pellecchia, Carmelo Russo and Luigi Tonino Marsella
Pharmaceuticals 2024, 17(12), 1728; https://doi.org/10.3390/ph17121728 - 20 Dec 2024
Viewed by 522
Abstract
Background: Drugged driving is associated with an increased risk of road accidents worldwide. In Italy, driving under the influence (DUI) of alcohol and drugs is a reason for driving disqualification or revocation of the driving license. Drivers charged with driving under the influence [...] Read more.
Background: Drugged driving is associated with an increased risk of road accidents worldwide. In Italy, driving under the influence (DUI) of alcohol and drugs is a reason for driving disqualification or revocation of the driving license. Drivers charged with driving under the influence of alcohol and drugs must attend a Local Medical Commission (LMC) to undergo mandatory examinations to regain the suspended license. Our study mainly aims to report on the analysis performed on hair samples collected from 7560 drivers who had their licenses suspended for drugged or drunk driving between January 2019 and June 2024. Methods: A rapid, sensitive, and selective method for the determination of ethyl glucuronide in hair by UPLC/MS-MS was developed and fully validated. Results: The most frequently detected substances were cocaine (ecgonine methyl ester, norcocaine, and benzoylecgonine) and cannabinoids (Δ9-tetrahydrocannabinol, cannabidiol, and cannabinol), followed by opiates (codeine, morphine, and 6-MAM), methadone (EDDP), and amphetamines (amphetamine, methamphetamine, MDA, MDMA, and MDEA). To perform a more in-depth analysis, we also compared hair color with the drug classes that tested positive. The results showed a significant prevalence of dark hair that tested positive for one or more substances, followed by gray/white hair and light hair. Conclusions: Our study provides an interesting and alarming insight into drug exposure in the general population with serious public health threats, discussing the main aspects of hair matrix analysis and focusing on its advantages and reliability in the interpretation of results. Full article
(This article belongs to the Special Issue Toxicological Effects of Drug Abuse and Its Consequences on Health)
►▼ Show Figures

Figure 1

20 pages, 3844 KiB  
Article
Inhibition of TFAM-Mediated Mitophagy by Oroxylin A Restored Sorafenib Sensitivity Under Hypoxia Conditions in HepG2 Cells
by Shufan Ji, Xuefen Xu, Yujia Li, Sumin Sun, Qiuyu Fu, Yangling Qiu, Shuqi Wang, Siwei Xia, Feixia Wang, Feng Zhang, Ji Xuan and Shizhong Zheng
Pharmaceuticals 2024, 17(12), 1727; https://doi.org/10.3390/ph17121727 - 20 Dec 2024
Viewed by 576
Abstract
Background: Liver cancer treatment encounters considerable therapeutic challenges, especially because hypoxic microenvironments markedly reduce sensitivity to chemotherapeutic agents. TFAM (mitochondrial transcription factor A) plays a crucial role in maintaining mitochondrial function. Oroxylin A (OA), a flavonoid with potential therapeutic properties, demonstrated prospects in [...] Read more.
Background: Liver cancer treatment encounters considerable therapeutic challenges, especially because hypoxic microenvironments markedly reduce sensitivity to chemotherapeutic agents. TFAM (mitochondrial transcription factor A) plays a crucial role in maintaining mitochondrial function. Oroxylin A (OA), a flavonoid with potential therapeutic properties, demonstrated prospects in cancer treatment. However, the mechanism of the sensitizing effect of OA on cancer cells has not been elucidated. Methods: MTT assays were utilized to evaluate a hypoxia-induced resistance model. Plate colony formation assays, TEM, and JC-1 staining were used to examine the effects of siTFAM on proliferation and mitochondrial damage of HepG2 cells. Cox8-EGFP-mCherry plasmid transfection, LysoTracker and MitoTracker colocalization analysis, and WB were conducted to evaluate the influence of OA on mitophagy. The effect of OA on p53 ubiquitination levels was investigated by Co-IP and the CHX chase assay. A mouse xenograft tumor model was utilized to assess the therapeutic effect of OA on HepG2 cells in vivo. Results: OA significantly improved the inhibitory effect of sorafenib by inhibiting mitophagy on HepG2 cells in in vitro and in vivo models. Notably, the molecular docking and thermal shift assays indicated a clear binding of OA and TFAM. Further research revealed that OA suppressed p53 acetylation and promoted its degradation by downregulating TFAM expression, which ultimately inhibited mitophagy in hypoxia. Conclusions: OA has demonstrated the potential to enhance the efficacy of sorafenib treatment for liver cancer, and TFAM may be one of its targets. Full article
(This article belongs to the Section Natural Products)
►▼ Show Figures

Graphical abstract

12 pages, 4449 KiB  
Review
The Interaction of Histamine H3 and Dopamine D1 Receptors on Hyperkinetic Alterations in Animal Models of Parkinson’s Disease
by Alberto Avila-Luna, Antonio Verduzco-Mendoza, Adriana Olmos-Hernández, José Luis Cortes-Altamirano, Alfonso Alfaro-Rodríguez, José-Antonio Arias-Montaño and Antonio Bueno-Nava
Pharmaceuticals 2024, 17(12), 1726; https://doi.org/10.3390/ph17121726 - 20 Dec 2024
Viewed by 536
Abstract
Parkinson’s disease is associated with the loss of more than 40% of dopaminergic neurons in the substantia nigra pars compacta. One of the therapeutic options for restoring striatal dopamine levels is the administration of L-3,4-dihydroxyphenylalanine (L-Dopa). However, Parkinson’s disease patients on long-term L-Dopa [...] Read more.
Parkinson’s disease is associated with the loss of more than 40% of dopaminergic neurons in the substantia nigra pars compacta. One of the therapeutic options for restoring striatal dopamine levels is the administration of L-3,4-dihydroxyphenylalanine (L-Dopa). However, Parkinson’s disease patients on long-term L-Dopa therapy often experience motor complications, such as dyskinesias. L-Dopa-induced dyskinesias (LIDs) manifest as abnormal involuntary movements and are produced by elevated striatal dopamine levels, which lead to increased activity of the basal ganglia direct striato-nigral pathway. Dopamine D1 receptors are more than 95% confined to neurons of the direct pathway, where they colocalize with histamine H3 receptors. There is evidence of functional interactions between D1 and H3 receptors, and here we review the consequences of these interactions on LIDs. Full article
(This article belongs to the Special Issue Dopamine and Serotonin Receptors: Selective or Multitarget Ligands for the Treatment of Central Nervous System Diseases)
►▼ Show Figures

Figure 1

26 pages, 1545 KiB  
Review
Natural Antimicrobial Peptides and Their Synthetic Analogues for Effective Oral Microflora Control and Oral Infection Treatment—The Role of Ceragenins in the Development of New Therapeutic Methods
by Michał Czarnowski, Urszula Wnorowska, Milena Łuckiewicz, Ewelina Dargiewicz, Jakub Spałek, Sławomir Okła, Beata Sawczuk, Paul B. Savage, Robert Bucki and Ewelina Piktel
Pharmaceuticals 2024, 17(12), 1725; https://doi.org/10.3390/ph17121725 - 20 Dec 2024
Viewed by 884
Abstract
Oral diseases, both acute and chronic, of infectious or non-infectious etiology, represent some of the most serious medical problems in dentistry. Data from the literature increasingly indicate that changes in the oral microbiome, and therefore, the overgrowing of pathological microflora, lead to a [...] Read more.
Oral diseases, both acute and chronic, of infectious or non-infectious etiology, represent some of the most serious medical problems in dentistry. Data from the literature increasingly indicate that changes in the oral microbiome, and therefore, the overgrowing of pathological microflora, lead to a variety of oral-localized medical conditions such as caries, gingivitis, and periodontitis. In recent years, compelling research has been devoted to the use of natural antimicrobial peptides as therapeutic agents in the possible treatment of oral diseases. This review focuses on the potential of ceragenins (CSAs), which are lipid analogs of natural antimicrobial peptides, as molecules for the development of new methods for the prevention and treatment of oral diseases. Studies to date indicate that ceragenins, with their spectrum of multidirectional biological activities, including antimicrobial, tissue regeneration-stimulating, anti-inflammatory, and immunomodulatory properties, are strong candidates for further development of oral formulations. However, many of the beneficial properties of ceragenins require confirmation in experimental conditions reproducing the oral environment to fully determine their application potential. Their transition to practical use also requires more advanced testing of these molecules in clinical trials, which have only been conducted in limited numbers to date. Full article
(This article belongs to the Section Natural Products)
►▼ Show Figures

Figure 1

29 pages, 1312 KiB  
Review
Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances
by Liangtao Zhao, Haolan Tang and Zhangjun Cheng
Pharmaceuticals 2024, 17(12), 1724; https://doi.org/10.3390/ph17121724 - 20 Dec 2024
Viewed by 1207
Abstract
Liver fibrosis is a progressive scarring process primarily caused by chronic inflammation and injury, often closely associated with viral hepatitis, alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), drug-induced liver injury, and autoimmune liver disease (AILD). Currently, there are very few clinical [...] Read more.
Liver fibrosis is a progressive scarring process primarily caused by chronic inflammation and injury, often closely associated with viral hepatitis, alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), drug-induced liver injury, and autoimmune liver disease (AILD). Currently, there are very few clinical antifibrotic drugs available, and effective targeted therapy is lacking. Recently, emerging antifibrotic drugs and immunomodulators have shown promising results in animal studies, and some have entered clinical research phases. This review aims to systematically review the molecular mechanisms underlying liver fibrosis, focusing on advancements in drug treatments for hepatic fibrosis. Furthermore, since liver fibrosis is a progression or endpoint of many diseases, it is crucial to address the etiological treatment and secondary prevention for liver fibrosis. We will also review the pharmacological treatments available for common hepatitis leading to liver fibrosis. Full article
(This article belongs to the Section Pharmacology)
►▼ Show Figures

Graphical abstract

17 pages, 2692 KiB  
Article
Simple and Efficient Synthesis of N-Succinimidyl-4-[18F]fluorobenzoate ([18F]SFB)—An Important Intermediate for the Introduction of Fluorine-18 into Complex Bioactive Compounds
by Viktoriya V. Orlovskaya, Olga S. Fedorova, Nikolai B. Viktorov and Raisa N. Krasikova
Pharmaceuticals 2024, 17(12), 1723; https://doi.org/10.3390/ph17121723 - 20 Dec 2024
Viewed by 638
Abstract
Background: N-succinimidyl-[18F]fluorobenzoate ([18F]SFB) is commonly prepared through a three-step procedure starting from [18F]fluoride ion. A number of methods for the single-step radiosynthesis of [18F]SFB have been introduced recently, including the radiofluorination of diaryliodonium [...] Read more.
Background: N-succinimidyl-[18F]fluorobenzoate ([18F]SFB) is commonly prepared through a three-step procedure starting from [18F]fluoride ion. A number of methods for the single-step radiosynthesis of [18F]SFB have been introduced recently, including the radiofluorination of diaryliodonium salts and the Cu-mediated 18F-fluorination of pinacol aryl boronates and aryl tributyl stannanes, but they still have the drawbacks of lengthy product purification procedures. In the present work, two approaches for the direct labeling of [18F]SFB from diaryliodonium (DAI) salt (4) and pinacol aryl boronate (6) are evaluated, with a major focus on developing a fast and simple SPE-based purification procedure. Methods: DAI salt precursor 6 was labeled employing the common “minimalist” approach with a two-step reaction heating sequence. The Cu-mediated radiofluorination of 4 was accomplished using Bu4NOTf as a phase transfer catalyst for the elution of [18F]fluoride, followed by radiofluorination in the same solvent. Several types of SPE cartridges were tested in the elution and SPE procedures. Results: The Cu-mediated 18F-fluorination of the pinacol aryl boronate precursor afforded a higher RCC of 56 ± 3% (n = 7), making it better suited for the one-pot synthesis of [18F]SFB. SPE-based purification was achieved using cation exchange and reverse-phase polymer resin cartridges, connected in series. In a full-batch test, [18F]SFB was obtained with an RCY of 30% (n. d. c.), RCP > 99%, Am 96–155 GBq/µmol, and a synthesis time of ≤35 min. Conclusions: Compared to other published methods, [18F]SFB production via the Cu-mediated radiofluorination of pinacol aryl boronate precursor provides significant time and cost savings, coupled with an ease of implementation. Full article
(This article belongs to the Special Issue Innovative Approaches to Radiopharmaceuticals: Advances in Design, Labeling, and Applications)
►▼ Show Figures

Figure 1

14 pages, 931 KiB  
Case Report
Delayed Onset of Thrombotic Microangiopathy (TMA) upon Prolonged Carfilzomib Therapy in Multiple Myeloma: A Case Report and Comprehensive Review
by Andrea Ceglédi, Ágnes Király, Andrea Várkonyi, Szabolcs Tasnády, Hajnalka Andrikovics, Mónika Fekete, Bálint G. Szabó, Zsuzsanna Szemlaky, Ágnes Szilágyi, György Sinkovits, Zoltán Prohászka, Marienn Réti and Gábor Mikala
Pharmaceuticals 2024, 17(12), 1722; https://doi.org/10.3390/ph17121722 - 20 Dec 2024
Viewed by 569
Abstract
Background: Thrombotic microangiopathy (TMA) is a potentially life-threatening complication associated with carfilzomib, a proteasome inhibitor approved for treating multiple myeloma. TMA typically presents within the initial months of treatment; however, delayed onset is rare and poses significant diagnostic challenges. Methods: We conducted a [...] Read more.
Background: Thrombotic microangiopathy (TMA) is a potentially life-threatening complication associated with carfilzomib, a proteasome inhibitor approved for treating multiple myeloma. TMA typically presents within the initial months of treatment; however, delayed onset is rare and poses significant diagnostic challenges. Methods: We conducted a retrospective analysis of the medical records of a 47-year-old Caucasian woman diagnosed with IgA kappa myeloma who developed signs and symptoms consistent with TMA eleven months after the initiation of carfilzomib therapy and already in ongoing very good partial remission. Results: The clinical presentation included an acute onset of weakness, dizziness, somnolence, diffuse bruising, oliguria, jaundice, severe thrombocytopenia, and acute kidney injury. An immediate workup raised a strong suspicion for TMA, confirmed by laboratory findings of schistocytosis and complement activation. Following the immediate discontinuation of carfilzomib, the patient underwent 18 plasmapheresis (PEX) sessions and received supportive fresh frozen plasma transfusions, which resulted in the complete remission of TMA symptoms without the need for complement inhibitory therapy. Conclusions: The need for ongoing monitoring for TMA throughout carfilzomib therapy, regardless of treatment duration, is emphasized. Early diagnosis and intervention, including drug discontinuation and the timely initiation of PEX, are crucial for patient recovery. Full article
(This article belongs to the Special Issue Novel Therapeutics in Hematology)
►▼ Show Figures

Figure 1

26 pages, 1442 KiB  
Systematic Review
Theranostics in Renal Cell Carcinoma—A Step Towards New Opportunities or a Dead End—A Systematic Review
by Katarzyna Jóźwik-Plebanek, Marek Saracyn, Maciej Kołodziej, Olga Kamińska, Adam Daniel Durma, Weronika Mądra, Katarzyna Agnieszka Gniadek-Olejniczak, Marek Dedecjus, Jakub Kucharz, Rafał Stec and Grzegorz Kamiński
Pharmaceuticals 2024, 17(12), 1721; https://doi.org/10.3390/ph17121721 - 19 Dec 2024
Viewed by 675
Abstract
Background: Renal cell carcinoma is one of the most aggressive urogenital malignancies, with an increasing number of cases worldwide. The majority of cases are diagnosed at an advanced stage, as this form of growth is typically silent. An accurate evaluation of the extent [...] Read more.
Background: Renal cell carcinoma is one of the most aggressive urogenital malignancies, with an increasing number of cases worldwide. The majority of cases are diagnosed at an advanced stage, as this form of growth is typically silent. An accurate evaluation of the extent of the disease is crucial for selecting the most appropriate treatment approach. Nuclear medicine imaging is increasingly being applied in oncological diagnostics, prompting ongoing research into renal cell carcinoma markers that could serve as a foundation for theranostic approaches in this disease. Positron emission tomography/computed tomography imaging with prostate-specific membrane antigen (PSMA) ligands has already demonstrated successful utility in diagnosis of other cancers, including prostate cancer and gliomas. Emerging evidence of high sensitivity and specificity in detecting renal cell carcinoma lesions provides a suitable foundation for its application in both the diagnosis and subsequent management of this malignancy. Methods: This systematic review synthesizes the current scientific evidence on the molecular imaging of renal cell carcinoma using PSMA ligands, emphasizing the potential future applications of this imaging marker in theranostic approaches. Results and Conclusions: Based on a systematic review of the literature, it appears that PET/CT with PSMA ligands has the potential to surpass traditional imaging techniques in diagnostic accuracy while also providing valuable prognostic information. Full article
(This article belongs to the Special Issue Modern Approach to Neuroendocrine Neoplasms Diagnosis and Treatment)
►▼ Show Figures

Graphical abstract

14 pages, 2799 KiB  
Article
Advances in Canine Anesthesia: Physiologically Based Pharmacokinetic Modeling for Predicting Propofol Plasma Profiles in Canines with Hepatic Impairment
by Lucas Wamser Fonseca Gonzaga, Beatriz Monte Egito, João Bosco Costa Coelho, Gabriela Pereira Souza, Frederico Severino Martins and Marcos Ferrante
Pharmaceuticals 2024, 17(12), 1720; https://doi.org/10.3390/ph17121720 - 19 Dec 2024
Viewed by 487
Abstract
Background: A PBPK model allows the prediction of the concentration of drug amounts in different tissues and organs over time and can be used to simulate and optimize different therapeutic protocols in healthy and sick individuals. The objective of this work was [...] Read more.
Background: A PBPK model allows the prediction of the concentration of drug amounts in different tissues and organs over time and can be used to simulate and optimize different therapeutic protocols in healthy and sick individuals. The objective of this work was to create a PBPK model to predict propofol doses for healthy canines and canines with hepatic impairment. Methods: The study methodology was divided into two major phases, in which the first phase consisted of creating the PBPK model for healthy canines, and in the second phase, this model was adjusted for canines with hepatic impairment. The model for healthy canines presented good predictive performance, evidenced by the value of the performance measure of the geometric mean fold error that ranged from 0.8 to 1.25, meeting the double error criterion. The simulated regimen for healthy canines, i.e., of 5 mg/kg (administered as a bolus) followed by a continuous infusion at a rate of 0.13 mg/kg/min, was sufficient and ensured that all simulated subjects achieved the target plasma concentration. Canines with 60% and 40% liver function had infusion rate adjustments to ensure that individuals did not exceed the therapeutic window for maintenance of anesthesia. Results: The results presented in this manuscript are suggestive of the effectiveness and practicality of a PBPK model for propofol in canines, with a particular focus on hepatic impairment. Full article
(This article belongs to the Section Pharmacology)
►▼ Show Figures

Figure 1

21 pages, 5025 KiB  
Article
Transcriptome Analysis Reveals the Mechanism of Y0-C10-HSL on Biofilm Formation and Motility of Pseudomonas aeruginosa
by Deping Tang, Yali Liu, Huihui Yao, Yanyan Lin, Yanpeng Xi, Mengjiao Li and Aihong Mao
Pharmaceuticals 2024, 17(12), 1719; https://doi.org/10.3390/ph17121719 - 19 Dec 2024
Viewed by 550
Abstract
Background: Pseudomonas aeruginosa (P. aeruginosa) is a type of pathogen that takes advantage of opportunities to infect and form biofilm during infection. Inhibiting biofilm formation is a promising approach for the treatment of biofilm-related infections. Methods: Here, Y0-C10-HSL (N-cyclopentyl-n-decanamide) was [...] Read more.
Background: Pseudomonas aeruginosa (P. aeruginosa) is a type of pathogen that takes advantage of opportunities to infect and form biofilm during infection. Inhibiting biofilm formation is a promising approach for the treatment of biofilm-related infections. Methods: Here, Y0-C10-HSL (N-cyclopentyl-n-decanamide) was designed, synthesized, and tested for its effect on biofilm formation, motility, and the Caenorhabditis elegans (C. elegans) survival assay. In addition, the molecular mechanism of Y0-C10-HSL on P. aeruginosa biofilm formation was explored using transcriptome analysis. Results: At a concentration of 200 μmol/L Y0-C10-HSL, biofilm and exopolysaccharides were decreased by 38.5% and 29.3%, respectively; Y0-C10-HSL effectively dispersed the pre-formed biofilm and inhibited the motility ability of P. aeruginosa; and the C. elegans survival assay showed that Y0-C10-HSL was safe and provided protection to C. elegans against P. aeruginosa infection (the survival rates of C. elegans were higher than 74% and increased by 39%, 35.1%, and 47.5%, respectively, when treated with 200 μmol/L Y0-C10-HSL at 24, 48, and 80 h). Transcriptome analysis showed that 585 differentially expressed genes (DEGs) were found after treatment with 200 μmol/L Y0-C10-HSL, including 254 up-regulated DEGs and 331 down-regulated DEGs. The genes involved in the quorum sensing system and biofilm formation were down-regulated. Conclusions: Y0-C10-HSL inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa through down-regulated genes related to quorum sensing pathways and biofilm formation. These findings provide a theoretical foundation for the treatment and prevention of antibiotic resistance in clinical and environmental microorganisms such as P. aeruginosa. Full article
(This article belongs to the Section Biopharmaceuticals)
►▼ Show Figures

Figure 1

5 pages, 210 KiB  
Editorial
Advances in Pharmaceutical Science in Electrochemotherapy: A Tribute to Prof. Jolanta Saczko
by Nina Rembiałkowska and Julita Kulbacka
Pharmaceuticals 2024, 17(12), 1718; https://doi.org/10.3390/ph17121718 - 19 Dec 2024
Viewed by 585
Abstract
This Special Issue is dedicated to the memory of Professor Jolanta Saczko (1964–2023), a remarkable leader whose guidance and dedication were instrumental in advancing electroporation-based research in Poland [...] Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Jolanta Saczko: Pharmaceutical Science in Electrochemotherapy)
20 pages, 6012 KiB  
Article
Novel Anthraquinone Derivatives and Their Complexes with Metal Ions with Anticancer Activity: Structure/Redox and Chelation Activity Correlations
by Olga Yu. Selyutina, Maya A. Ul’yanova, Olga A. Chinak, Viktor A. Timoshnikov, Lidiya G. Fedenok, Alexander A. Stepanov, Vadim V. Yanshole, Leonid V. Kulik, Sergey F. Vasilevsky, Nikolay E. Polyakov and George J. Kontoghiorghes
Pharmaceuticals 2024, 17(12), 1717; https://doi.org/10.3390/ph17121717 - 19 Dec 2024
Viewed by 554
Abstract
Background/Objectives: Some specific anthraquinone derivatives (AQs) are known to be used widely as effective chemotherapeutic agents in the treatment of cancer. However, their fundamental shortcoming is the high rate of cardiotoxicity observed in treated patients, which is thought to be caused by the [...] Read more.
Background/Objectives: Some specific anthraquinone derivatives (AQs) are known to be used widely as effective chemotherapeutic agents in the treatment of cancer. However, their fundamental shortcoming is the high rate of cardiotoxicity observed in treated patients, which is thought to be caused by the increase in production of reactive oxygen species (ROS) catalyzed by iron and copper. The development of improved AQs and other anticancer drugs with enhanced efficacy but reduced toxicity remains a high priority. The aim of this study was to evaluate the cytotoxic and ROS production effects of chelate iron and copper complexes of two novel AQs, namely 4-hydroxynaphto[2,3-h]cinnoline-7,12-dione (Q2) and 3-(hydroxymethyl)naphto[2,3-h]cinnoline-4,7,12(1H)-trione (Q3). Methods: The chelation ability of Q2 and Q3 was studied using NMR and UV–Vis spectroscopy. Cytotoxicity studies were carried out using the MTT assay. The influence of chelation on ROS production was studied using NMR spectroscopy in linoleic acid micelles. Results: It was found that only Q3 forms complexes with Fe(III) and Cu(II) ions, whereas Q2 does not demonstrate chelating properties. A cytotoxicity study revealed that Fe[Q3]3 significantly decreased the viability of lung cancer A549 cells, while Q3 and Cu[Q3]2 did not demonstrate cytotoxic properties in this cell line. Furthermore, the presence of Q3 lowered the rate of iron-induced lipid peroxidation in linoleic acid micelles. By contrast, Q2 did not influence the rate of lipid peroxidation, probably due to the absence of effective metal chelating ability. Conclusions: The high cytotoxic effects observed with the iron complex of Q3 against cancer cells in combination with a reduced rate of iron induced lipid peroxidation in the presence of Q3, make Q3 and its iron complex promising for further evaluation and use as chemotherapeutic agents in cancer. Full article
(This article belongs to the Special Issue Recent Advances in Cancer Diagnosis and Therapy)
►▼ Show Figures

Figure 1

14 pages, 7660 KiB  
Article
Boric Acid Protects the Uterus and Fallopian Tubes from Cyclophosphamide-Induced Toxicity in a Rat Model
by Enes Karaman and Adem Yavuz
Pharmaceuticals 2024, 17(12), 1716; https://doi.org/10.3390/ph17121716 - 19 Dec 2024
Viewed by 644
Abstract
Background/Objectives: Cyclophosphamide (CP) is widely used for treating various cancers and autoimmune diseases, but it causes damage to reproductive organs due to oxidative stress (OS) and inflammation. Boric acid (BA) has antioxidant properties that may help reduce OS, which is critical for [...] Read more.
Background/Objectives: Cyclophosphamide (CP) is widely used for treating various cancers and autoimmune diseases, but it causes damage to reproductive organs due to oxidative stress (OS) and inflammation. Boric acid (BA) has antioxidant properties that may help reduce OS, which is critical for preserving uterine functionality, particularly for cancer patients considering pregnancy after cryopreservation. This study aimed to determine whether BA could diminish CP-induced toxicity in the uterus and fallopian tubes (FT) using CP-induced toxicity in a rat model. Methods: Forty female Wistar rats, aged 18–20 weeks, were divided into four groups as follows: control, oral BA (OBR), CP, and CP plus OBR (CP + OBR). The toxicity was induced in the CP and CP + OBR groups with an initial dose of 200 mg/kg CP, followed by 8 mg/kg daily for 14 days. Rats in the OBR and CP + OBR groups received 20 mg/kg/day of BA. After the 16-day experiment, tissues were collected for analysis. Results: Histopathological and immunohistochemical assessments of IL-6 and HIF-1α expressions were used to evaluate inflammation and OS. The control, OBR, and CP + OBR groups maintained normal tissue features, while the CP group showed epithelial cell shedding, vacuolization, degenerative endometrial glands, lymphocyte infiltration, and reduced collagen fiber density. Elevated HIF-1α and IL-6 expressions in the uterus and FT indicated significant OS and inflammation. Conclusions: The study concluded that BA supplementation in CP-treated rats effectively reduced CP-induced uterine and FT damage, suggesting the potential protective role of BA in managing CP-associated toxicity. Full article
(This article belongs to the Special Issue Boron-Containing Compounds: Identification, Synthesis, Biological Actions and Pharmacology)
►▼ Show Figures

Graphical abstract

16 pages, 1359 KiB  
Article
In Silico Evaluation of Potential NDM-1 Inhibitors: An Integrated Docking and Molecular Dynamics Approach
by Eduvan Valencia, Mauricio Galvis, Jorge Nisperuza, Vladimir Ballesteros and Fredy Mesa
Pharmaceuticals 2024, 17(12), 1715; https://doi.org/10.3390/ph17121715 - 19 Dec 2024
Viewed by 941
Abstract
Background/Objectives: Non-fermenting Gram-negative bacteria are resistant to most antibiotics, due to the production of enzymes such as NDM-1. Faced with this challenge, computational methods have become essential for the design of NDM-1 carbapenemase inhibitors, optimizing both the time and cost of the development [...] Read more.
Background/Objectives: Non-fermenting Gram-negative bacteria are resistant to most antibiotics, due to the production of enzymes such as NDM-1. Faced with this challenge, computational methods have become essential for the design of NDM-1 carbapenemase inhibitors, optimizing both the time and cost of the development of new lead molecules. Methods: In this study, molecular docking and molecular dynamics (MD) simulations were performed in order to identify effective inhibitors against the NDM-1 enzyme. Protein preparation was carried out using UCSF Chimera and AutoDockTools 1.5.7, while ligands were prepared with MarvinSketch, Avogadro, and AutoDockTools 1.5.7. Molecular docking was run with AutoDock4 and AutoDock4Zn, determining that molecules M26 (−13.23 kcal/mol with AutoDock4 and −13.11 kcal/mol with AutoDockZn) and M25 (−10.61 kcal/mol with AutoDock4 and −11.18 kcal/mol with AutoDockZn) presented the best binding energy affinities with NDM-1. The M26 molecule formed six hydrogen bonds with the enzyme. Results: MD simulations, performed with GROMACS, indicated that the NDM-1-M26, NDM-1-M35, and NDM-1-M37 complexes showed conformational stability and flexibility. Conclusions: These results suggest that the M26, M37, and M35 ligands have significant potential as leading candidates in the development of new NDM-1 inhibitors, outperforming the antibiotic Meropenem in some respects. Full article
(This article belongs to the Special Issue Selected Papers from the 9th International Electronic Conference on Medicinal Chemistry (ECMC2023))
►▼ Show Figures

Figure 1

26 pages, 531 KiB  
Article
Age-Dependent Analysis of Suicidal Ideation, Suicide Attempts, and Suicides Associated with SSRI and SNRI Drugs Based on Pharmacovigilance Data
by Daria Schetz, Jacek Sein Anand, Łukasz Sein Anand and Ivan Kocić
Pharmaceuticals 2024, 17(12), 1714; https://doi.org/10.3390/ph17121714 - 19 Dec 2024
Viewed by 754
Abstract
Background: Antidepressants such as SSRIs and SNRIs are widely prescribed; however, significant concerns exist regarding psychiatric adverse drug reactions (ADRs), particularly suicidal ideation, suicide attempts, and completed suicides. This study analyzes pharmacovigilance (PhV) data from the EudraVigilance database to assess the frequency of [...] Read more.
Background: Antidepressants such as SSRIs and SNRIs are widely prescribed; however, significant concerns exist regarding psychiatric adverse drug reactions (ADRs), particularly suicidal ideation, suicide attempts, and completed suicides. This study analyzes pharmacovigilance (PhV) data from the EudraVigilance database to assess the frequency of psychiatric ADRs, including suicide-related events, associated with six commonly used antidepressants. Another aim of the study is to evaluate the utility of pharmacovigilance data in providing insights into real-world risks associated with medications, highlighting the importance of improving the ADR reporting system and ensuring the completeness and reliability of ADR reports. Methods: Data from December 2001 to September 2024 were analyzed for duloxetine, citalopram, escitalopram, fluoxetine, venlafaxine, and sertraline. Reports were categorized by age, gender, and source, focusing on psychiatric ADRs and suicide-related events, including completed suicides and suicide attempts. Results: Psychiatric ADRs accounted for a substantial portion of total reported ADRs for the studied antidepressants, ranging from 33.9% to 38.2%. Venlafaxine had the highest count of psychiatric ADRs (13,134 cases), with duloxetine showing the highest relative percentage (38.2%). Completed suicides were most frequent with venlafaxine (1635 cases), while the highest percentage relative to total ADRs was observed for fluoxetine and citalopram (6%). ADRs occurred more frequently in women, particularly for duloxetine (67%) and sertraline (61.3%), and suicide attempts were prevalent in patients aged 18–64, with notable incidence in the 0–17 age group. Conclusions: This study highlights the significant patterns, risks, and underreporting of psychiatric ADRs associated with commonly prescribed antidepressants. Using EudraVigilance data and a worst-case scenario approach, it reveals the extent of suicide-related ADRs, age and gender disparities, and the impact of incomplete reporting on risk assessment. Full article
(This article belongs to the Section Pharmacology)
►▼ Show Figures

Figure 1

16 pages, 1261 KiB  
Article
Immune Checkpoint Blockade Combined with AbnobaViscum® Therapy Is Linked to Improved Survival in Advanced or Metastatic Non-Small-Cell Lung Cancer Patients: A Registry Study in Accordance with the ESMO Guidance for Reporting Real-World Evidence
by Friedemann Schad, Anja Thronicke, Ralf-Dieter Hofheinz, Reinhild Klein, Patricia Grabowski, Shiao Li Oei, Hannah Wüstefeld and Christian Grah
Pharmaceuticals 2024, 17(12), 1713; https://doi.org/10.3390/ph17121713 - 18 Dec 2024
Viewed by 772
Abstract
Background: Recent advancements in cancer treatment have shown the potential of immune checkpoint blockade (ICB) plus Viscum album L. therapy in improving survival rates for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to investigate factors [...] Read more.
Background: Recent advancements in cancer treatment have shown the potential of immune checkpoint blockade (ICB) plus Viscum album L. therapy in improving survival rates for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to investigate factors associated with improved survival in NSCLC patients treated with a combination of ICB and abnobaViscum®. Methods: Patients with advanced or metastatic NSCLC from the accredited Network Oncology registry were included in this real-world data study adhering to ESMO-GROW criteria with ethics approval. Survival outcomes were compared between patients receiving ICB therapy alone versus those receiving combinational ICB plus abnobaViscum® therapy using Kaplan–Meier and multivariable Cox proportional hazard analysis. Results: Among 300 patients (median age 68 years; male/female ratio 1.19), 222 received ICB alone (CTRL group) and 78 received combinational therapy (COMB group). Overall survival was significantly prolonged in the COMB group by 7 months compared to CTRL (13.8 months vs. 6.8 months, p = 0.005) with a survival rate of 16.5% in the COMB group vs. 8.0% in the CTRL group. In programmed death-ligand 1 positive (≥1%) patients treated with first-line ICB, the addition of abnobaViscum® reduced the adjusted hazard of death by 75% (aHR: 0.25; 95%CI: 0.11–0.60, p = 0.02). Conclusions: The addition of abnobaViscum® to ICB is significantly associated with improved survival in patients with advanced or metastatic NSCLC patients, irrespective of age, stage, Eastern cooperative oncology group status, surgery, or radiation. Potential mechanisms include immune modulation, reduced primary ICB resistance, and tumor microenvironment modifications. The findings warrant further validation in randomized controlled trials or registry-based randomized controlled trials. Trial registration: The study was registered (DRKS00013335). Full article
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-183
Previous Issue
Next Issue
Back to TopTop