Article
Chemistry, Medicinal
Sarah Lazzaro, Mark A. West, Soraya Eatemadpour, Bo Feng, Manthena V. S. Varma, A. David Rodrigues, Csilla Temesszentandrasi-Ambrus, Peter Kovacs-Hajdu, Zsuzsanna Nerada, Zsuzsanna Gaborik, Chester Costales
Summary: This study evaluated the impact of potential IC50 discrepancies between two commonly utilized assay methods (cell-based and vesicle-based) on P-gp. Non-P-gp substrates showed good correlation between the two methods, while IC50s of P-gp substrates were lower in the vesicle assays. IC50s obtained from two independent laboratories using the same method showed good correlation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Sonia Saib, Xavier Delavenne
Summary: Inflammation can impact the expression and functionality of ABC transporters, leading to variability in drug response, especially for drugs with a narrow therapeutic index. Existing contradictory data and lack of standardization in the models used have resulted in a less conclusive interpretation of these findings.
Article
Medicine, Research & Experimental
Lara Garcia-Varela, Manuel Rodriguez-Perez, Antia Custodia, Rodrigo Moraga-Amaro, Nicola A. Colabufo, Pablo Aguiar, Tomas Sobrino, Rudi A. J. O. Dierckx, Aren van Waarde, Philip H. Elsinga, Gert Luurtsema
Summary: P-glycoprotein (P-gp) inducer MC111 increases P-gp functionality in the whole brain of rats, potentially offering a treatment option for neurodegenerative diseases.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Diogo Henrique Kita, Gisele Alves de Andrade, Juliana Morais Missina, Kahoana Postal, Viktor Kalbermatter Boell, Francielli Sousa Santana, Ingrid Fatima Zattoni, Isadora da Silva Zanzarini, Vivian Rotuno Moure, Fabiane Gomes de Moraes Rego, Geraldo Picheth, Emanuel Maltempi de Souza, David A. Mitchell, Suresh Ambudkar, Giovana Gioppo Nunes, Glaucio Valdameri
Summary: The study found that polyoxovanadates can serve as inhibitors of ABC drug transporters, selectively inhibiting P-glycoprotein with V-10 and V-18 being the most promising compounds.
Review
Multidisciplinary Sciences
Carlos Pilotto Heming, Wanjiru Muriithi, Lucy Wanjiku Macharia, Paulo Niemeyer Filho, Vivaldo Moura-Neto, Veronica Aran
Summary: Acquired resistance during cancer treatment is often caused by ABC transporters, such as P-gp, which export chemotherapeutic molecules and contribute to multidrug resistance. In addition to its role in drug resistance, P-gp may also have other functions and serve as a biomarker in cancer.
Article
Biochemistry & Molecular Biology
Shagufta Iqbal, Caitlin Flux, Deborah A. Briggs, Evelyne Deplazes, Jiansi Long, Ruth Skrzypek, Alice Rothnie, Ian D. Kerr, Richard Callaghan
Summary: Through the use of mutational analysis and computational modeling, the binding sites for the substrates vinblastine and rhodamine 123 on P-glycoprotein (Pgp) were successfully determined. Binding occurs in the central cavity and the lipid-protein interface, revealing the process of substrate internalization in Pgp.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Biochemistry & Molecular Biology
Sepehr Dehghani-Ghahnaviyeh, Karan Kapoor, Emad Tajkhorshid
Summary: This study used molecular dynamics simulations to investigate the ATP hydrolysis-induced conformational changes in Pgp nucleotide-binding domains (NBDs), revealing that ATP/ADP exchange induced conformational changes within the conserved signature motif of NBDs, resulting in relative orientational changes. Furthermore, putative hydrolysis-competent configurations were captured, with a conserved glutamate in the Walker-B motif acting as a catalytic base capturing a water molecule likely initiating ATP hydrolysis.
Article
Infectious Diseases
Bo Yang, Dongqiang Wang, Mingxiao Liu, Xiaodong Wu, Jigang Yin, Guan Zhu
Summary: The study aimed to generate host cells with resistance to specific anti-cryptosporidial drugs by transiently overexpressing the MDR1 gene. Results showed increased drug tolerance in host cells for certain compounds with varying effects on the anti-parasitic efficacy, highlighting the importance of understanding drug targets in parasite vs. host cells.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T. M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Summary: This study found that small changes in P-gp function caused by low doses of tariquidar could be detected by [F-18]MC225-K-1 values, confirming the high sensitivity of the radiotracer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Pharmacology & Pharmacy
Valerio Taggi, Mario Riera Romo, Micheline Piquette-Miller, Henriette E. Meyer zu Schwabedissen, Sibylle Neuhoff
Summary: Drug transporters are crucial for maintaining chemical balance and homeostasis in tissues, as well as for the absorption, distribution, and elimination of clinically important drugs. Diseases can alter the expression and function of drug transporters. However, there is limited knowledge on transporter regulation in critical protective barriers, which requires further research.
Article
Biochemistry & Molecular Biology
Keerthana Sasitharan, Hamzah Asad Iqbal, Foteini Bifsa, Aleksandra Olszewska, Kenneth J. Linton
Summary: The study investigates the role of hydrogen bonds and specific glutamines in drug recognition and transport by the ABCB1 efflux transporter. Results show that different glutamine mutations have varying effects on the transport of different drug classes, suggesting a complex mechanism of drug recognition. Surprisingly, some mutations improved drug transport, highlighting the intricate interactions within the drug binding pocket of ABCB1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Yanyan Ma, Zhanchen Guo, Chuanwen Fan, Jingran Chen, Shuxin Xu, Zhen Liu
Summary: This study developed aptamers that can target ABCG2 and reverse multidrug resistance, showing great potential in cancer diagnosis and treatment. The aptamers can specifically bind to human colorectal cancer stem cells and effectively reverse drug resistance in liver cancer cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiangyu Li, Xiaolian Li, Xingcai Yang, Chengxiang Lan, Ying Huang, Bin Jia
Summary: Microalgae are promising microorganisms for producing value-added products or developing sustainable environmental remediation approaches. This study investigated the ABC proteins of Chlamydomonas reinhardtii and identified 75 CrABCs, classifying them into eight subfamilies. The study provided insights into the evolutionary history and functional roles of CrABCs, supporting their involvement in heavy metal detoxification, lipid metabolism, and environmental adaptation.
Article
Medicine, Research & Experimental
Laust Moesgaard, Peter Reinholdt, Carsten Uhd Nielsen, Jacob Kongsted
Summary: Considerable effort has been devoted to the search for modulators of membrane transport proteins. This study focuses on the inhibitory effect of polysorbate 20 (PS20) on P-glycoprotein (P-gp) and aims to understand the underlying molecular mechanism. Molecular dynamics simulations revealed that the hydrophobic nature of PS20 drives its binding to the drug-binding domain of P-gp, resulting in the inhibition of the protein's function.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Lena Radtke, Aleksandra Majchrzak-Celinska, Charles Awortwe, Inga Vater, Inga Nagel, Susanne Sebens, Ingolf Cascorbi, Meike Kaehler
Summary: This study demonstrates the significance of ABCB1 in GBM cells, affecting the response to temozolomide and carmustine treatment, while ABCG2 plays a marginal role.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Dermatology
Arden M. Klinczar, Joel D. Griffies, Fiona L. Bateman, Robert D. Arnold, Shanese L. Jasper, Austin R. Brown
Summary: The study aimed to determine the stability of amikacin at 10 and 30 mg/mL concentrations in four topical solutions over a 56 day period. The results showed that amikacin maintained stability within TE, TC, NA, and ND solutions over 56 days, except when formulated at 10 mg/mL within TE.
VETERINARY DERMATOLOGY
(2022)
Article
Nutrition & Dietetics
Shelby C. C. Osburn, Paul A. A. Roberson, Jessica A. A. Medler, Jacob Shake, Robert D. D. Arnold, Nima Alamdari, Luke R. R. Bucci, Arianne Vance, Mastaneh Sharafi, Kaelin C. C. Young, Michael D. D. Roberts
Summary: The study showed that supplementation with multivitamins increased serum vitamin D, serum folate, and red blood cell omega-3 fatty acid levels in females. These results are limited to healthy females, and further research is needed to explore whether the supplement can affect metabolic disturbances in individuals with micronutrient deficiencies.
FRONTIERS IN NUTRITION
(2021)
Article
Engineering, Biomedical
Nicole L. Habbit, Benjamin Anbiah, Luke Anderson, Joshita Suresh, Iman Hassani, Matthew Eggert, Andrew Brannen, Joshua Davis, Yuan Tian, Balabhaskar Prabhakarpandian, Peter Panizzi, Robert D. Arnold, Elizabeth A. Lipke
Summary: In this study, a three-dimensional in vitro prostate cancer tissue model was established and characterized based on xenograft tumor stiffness. The model can mimic the progression of prostate cancer and provide a foundation for future studies on cancer progression and drug development.
ACTA BIOMATERIALIA
(2022)
Article
Pharmacology & Pharmacy
Hamad Alrbyawi, Ishwor Poudel, Manjusha Annaji, Sai H. S. Boddu, Robert D. Arnold, Amit K. Tiwari, R. Jayachandra Babu
Summary: In this study, a pH-sensitive liposomal system was used to deliver daunorubicin to melanoma cells, resulting in enhanced cytotoxic effects. The liposomes exhibited high drug encapsulation efficiency and rapid release at acidic pH, leading to significantly higher cytotoxicity compared to conventional daunorubicin or liposomes.
Article
Biochemistry & Molecular Biology
Hamad Alrbyawi, Sai H. S. Boddu, Ishwor Poudel, Manjusha Annaji, Nur Mita, Robert D. Arnold, Amit K. Tiwari, R. Jayachandra Babu
Summary: This study developed a co-delivery system of daunorubicin and cardiolipin encapsulated in thermosensitive liposomes for the treatment of breast cancer. The liposomes exhibited high drug encapsulation efficiency, small size, and rapid release under mild hyperthermia, resulting in significantly higher cytotoxicity against breast cancer cells compared to daunorubicin or conventional liposomes. This research lays the foundation for future development of liposomal co-delivery systems for breast cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Reproductive Biology
Jean M. Feugang, Ghassan M. Ishak, Matthew W. Eggert, Robert D. Arnold, Orion S. Rivers, Scott T. Willard, Peter L. Ryan, Eduardo L. Gastal
Summary: Despite advancements in assisted reproductive techniques, there is still a need for rapid and minimally invasive in situ approaches to enhance female fertility. Researchers synthesized clinically relevant liposome nanoparticles and injected them into ovarian follicles of mares, achieving successful intrafollicular binding and migration of liposomes between different cell layers. Furthermore, the potential for intracellular delivery of nanoparticles was confirmed in porcine follicle wall cell types.
Article
Biochemistry & Molecular Biology
Ishwor Poudel, Manjusha Annaji, Fajar Setyo Wibowo, Robert D. Arnold, Oladiran Fasina, Brian Via, Vijaya Rangari, Maria Soledad Peresin, Forrest Smith, Muralikrishnan Dhanasekaran, Amit K. Tiwari, R. Jayachandra Babu
Summary: This study investigates the preparation of an inclusion complex of Hispolon with Sulfobutylether-beta-cyclodextrin (SBE beta CD) and the formulation of Hispolon-SBE beta CD trapped within sterically stabilized liposomes (HSC-SL). The results show that HSC-SL exhibits enhanced anticancer activity against melanoma cell lines and sustained drug release compared to Hispolon liposomes and Hispolon-SBE beta CD liposomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Suman Mazumder, Taraswi Mitra Ghosh, Ujjal K. Mukherjee, Sayak Chakravarti, Farshad Amiri, Razan S. Waliagha, Farnaz Hemmati, Panagiotis Mistriotis, Salsabil Ahmed, Isra Elhussin, Ahmad-Bin Salam, Windy Dean-Colomb, Clayton Yates, Robert D. Arnold, Amit K. Mitra
Summary: Prostate cancer (PCa) is a major cause of cancer deaths in US men. Drug resistance and specific cancer subtypes, such as epithelial-to-mesenchymal transdifferentiation (EMT) and neuroendocrine PCa (NEPC), pose significant challenges in PCa treatment. In this study, a computational prediction algorithm called secDrug identified potential secondary drugs for advanced-stage PCa. The proof-of-concept drug FK866, which targets NAMPT, showed promise in inhibiting drug resistance and stemness in PCa. The study also demonstrated the effects of FK866 on tumor metastasis, cell migration, and invasion, as well as regulation of genes associated with cancer stemness. The development pipeline introduced in this study has the potential to improve the management of lethal PCa.
Article
Biochemistry & Molecular Biology
Joshua T. T. Davis, Taraswi Mitra Ghosh, Suman Mazumder, Amit Mitra, Richard Curtis Bird, Robert D. D. Arnold
Summary: Maximum tolerable dosing (MTD) has been the traditional standard for aggressive cancers, but alternative dosing strategies are gaining attention due to their improved toxicity profiles and unique mechanisms. This study investigated whether extended exposure (EE) topotecan could prevent drug resistance and improve long-term drug sensitivity. The findings showed that EE topotecan had a higher barrier to resistance compared to MTD topotecan, maintaining consistent efficacy and a less aggressive malignant phenotype. Transcriptomic analysis revealed differences in epithelial-mesenchymal transition (EMT), efflux pumps, and topoisomerases between the two dosing strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Veterinary Sciences
Rebecca Kennerly, Amanda E. Coleman, Shanese L. Jasper, Robert D. Arnold, Benjamin M. Brainard
Summary: This study evaluated the effect of orally administered pimobendan on platelet function in healthy adult cats. The results showed that pimobendan did not have a significant inhibitory effect on platelet function in cats at two clinically relevant dosages.
AMERICAN JOURNAL OF VETERINARY RESEARCH
(2023)
Article
Veterinary Sciences
Annabelle Vigneault, Natalie D. Mylniczenko, Robert D. Arnold, Shanese L. Jasper-Trotter, Noemie Summa, Catherine Rousseau, Claire Vergneau-Grosset
Summary: Two adult male leopard sharks (Triakis semifasciata) under managed care were diagnosed with suspected dilated cardiomyopathy. Treatment with oral pimobendan resulted in improved cardiac function, increased appetite, and weight gain in the sharks. Long-term use of pimobendan did not cause any adverse effects.
JOURNAL OF ZOO AND WILDLIFE MEDICINE
(2023)
Article
Medicine, Research & Experimental
Ishwor Poudel, Manjusha Annaji, Chu Zhang, Peter R. Panizzi, Robert D. Arnold, Amal Kaddoumi, Rajesh H. Amin, Seungjong Lee, Nima Shamsaei, R. Jayachandra Babu
Summary: A surgically implantable device is a necessary treatment option for millions worldwide with orthopedic injuries. The use of additive manufacturing has enabled the customized fabrication of orthopedic implants with surface modifications. This study investigates the application of laser powder bed fusion to create 3D-printed implants functionalized with antimicrobial coatings to treat postsurgical infections.
MOLECULAR PHARMACEUTICS
(2023)
Article
Engineering, Biomedical
Nicole L. Habbit, Benjamin Anbiah, Joshita Suresh, Luke Anderson, Megan L. Davies, Iman Hassani, Taraswi M. Ghosh, Michael W. Greene, Balabhaskar Prabhakarpandian, Robert D. Arnold, Elizabeth A. Lipke
Summary: Using a 3D-engineered prostate cancer (PCa) tissue model, this study reveals that the incorporation of fibroblasts promotes PCa aggression by increasing proliferation, significant matrix remodeling, and enrichment of tumorigenic hallmark gene sets. Fibroblasts play an elevated role in indolent disease states and may contribute to the switch from androgen-dependent to castration-resistant PCa.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Pharmacology & Pharmacy
Elizabeth W. Covington, Shaneese L. Jasper-Trotter, Robert D. Arnold, Raj Amin, Susan Egbert, Allison Chung
Summary: High-dose vitamin D3 supplementation (10 000 IU/kg, max. 400 000 IU) significantly increased 25(OH)D3 levels in critically ill pediatric patients.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2023)
Review
Oncology
Manjusha Annaji, Ishwor Poudel, Sai H. S. Boddu, Robert D. Arnold, Amit K. Tiwari, R. Jayachandra Babu
Summary: Resveratrol, a natural polyphenol with therapeutic activities, faces limitations such as poor water solubility and short biological half-life. Recent studies suggest that Resveratrol nanoparticles have overcome these limitations and significantly enhanced its anticancer activity.