Review
Medicine, General & Internal
Alexa N. Bramall, E. S. Anton, Kristopher T. Kahle, Peter E. Fecci
Summary: Congenital or acquired hydrocephalus can significantly impact patients' quality of life. Current treatment methods are prone to failure and infection, so researchers aim to improve treatment outcomes through further understanding of cerebrospinal fluid pathways.
Article
Pharmacology & Pharmacy
Youssif Budagaga, Ziba Sabet, Yu Zhang, Eva Novotna, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: Tazemetostat is a unique multispecific chemosensitizer that can inhibit multiple ABC transporters and enhance the synergistic effect of chemotherapy by inducing apoptosis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Neurosciences
Lauren M. Hablitz, Maiken Nedergaard
Summary: The glymphatic system in the brain plays a key role in regulating interstitial fluid movement, waste clearance, and potentially brain immunity. Through the glymphatic system, there is potential to alter the local and global transport of signaling molecules and metabolites. Additionally, evidence suggests there is cross talk among the glymphatic system, cardiovascular system, gastrointestinal tract, and lymphatic system.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ziba Sabet, Dimitrios Vagiannis, Youssif Budagaga, Yu Zhang, Eva Novotna, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: This study provides a comprehensive overview of the pharmacokinetic drug-drug interactions of talazoparib and introduces it as an efficient multidrug resistance antagonist.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Parul Sharma, Navneet Singh, Siddharth Sharma
Summary: This study assessed the impact of ABC transporter gene variants on the prognosis and clinical outcomes of lung cancer patients. The results showed that certain gene variants were associated with poor survival outcomes, suggesting that genotype testing is essential for predicting prognosis in lung cancer patients.
JOURNAL OF GENE MEDICINE
(2023)
Article
Endocrinology & Metabolism
Skylar E. Johnson, Colin D. McKnight, Lori C. Jordan, Daniel O. Claassen, Spencer Waddle, Chelsea Lee, Maria Garza, Niral J. Patel, L. Taylor Davis, Sumit Pruthi, Paula Trujillo, Rohan Chitale, Matthew Fusco, Manus J. Donahue
Summary: The study revealed an increase in choroid plexus perfusion with reduced cortical perfusion, indicating an inverse association between choroid plexus and cortical perfusion.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Endocrinology & Metabolism
Jarrod J. Eisma, Colin D. McKnight, Kilian Hett, Jason Elenberger, Alexander K. Song, Adam J. Stark, Daniel O. Claassen, Manus J. Donahue
Summary: This study evaluated perfusion of the choroid plexus and cerebrospinal fluid flow in healthy adults. The findings showed that choroid plexus volume increased and perfusion decreased with age. Additionally, there were changes in total blood flow and cerebrospinal fluid flow with age. These findings have important implications for the understanding of CSF circulatory dysfunction in neurodegenerative and cerebrovascular diseases.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Immunology
Federico E. Turkheimer, Noha Althubaity, Julia Schubert, Maria A. Nettis, Oliver Cousins, Danai Dima, Valeria Mondelli, Edward T. Bullmore, Carmine Pariante, Mattia Veronese
Summary: The studies suggest that peripheral inflammation may lead to a reduction in blood-brain barrier permeability, disrupting brain homeostasis and inducing depressive symptoms.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Pharmacology & Pharmacy
Dimitrios Vagiannis, Yu Zhang, Youssif Budagaga, Eva Novotna, Adam Skarka, Sarah Kammerer, Jan-Heiner Kuepper, Jakub Hofman
Summary: This study suggests that alisertib is a drug candidate with minimal potential for pharmacokinetic drug-drug interactions and multidrug resistance. Furthermore, alisertib has shown to enhance the effectiveness of anticancer drugs without impairing their activity in resistant cells. These findings provide important information for clinical use of alisertib.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Chemistry, Physical
Damian Krzyzanowski, Marcin Kruszewski, Agnieszka Grzelak
Summary: Silver nanoparticles (AgNPs) have unique properties that have attracted significant attention, showing antibacterial, antifungal, and anticancer properties. However, they can also exhibit cytotoxic effects and modulate the activity and expression of ABC transporters.
Article
Pharmacology & Pharmacy
Chung-Pu Wu, Sung-Han Hsiao, Yu-Shan Wu
Summary: The overexpression of human ATP-binding cassette (ABC) transporters in cancer cells can lead to multidrug resistance (MDR), which poses a significant obstacle to chemotherapy. Currently, there are no approved drugs specifically designed to treat multidrug-resistant cancers. However, drug repurposing has emerged as a practical approach to discover effective modulators of drug transporters.
DRUG RESISTANCE UPDATES
(2023)
Article
Biochemistry & Molecular Biology
Kelli Monteiro da Costa, Leonardo Freire-de-Lima, Leonardo Marques da Fonseca, Jose Osvaldo Previato, Lucia Mendonca-Previato, Raphael do Carmo Valente
Summary: Multidrug resistance (MDR) and induction of metastasis are challenges in cancer chemotherapy. The ABC transporters play a role in MDR, while metastasis is associated with epithelial-mesenchymal transition (EMT). The study showed increased expression of ABCB1 and ABCC1 during EMT, with ABCC1 inhibitors partially inhibiting EMT-marker snail.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Tessa Peck, Connor Davis, Georgia Lenihan-Geels, Maddie Griffiths, Sam Spijkers-Shaw, Olga V. Zubkova, Anne Camille La Flamme
Summary: This study investigates the use of a novel HS-mimetic, Tet-29, in an animal model of MS. Tet-29 significantly reduced lymphocyte accumulation in the central nervous system and decreased disease severity in experimental autoimmune encephalomyelitis. The disease-modifying effect of Tet-29 was associated with a rescue of BBB integrity and inhibition of activated lymphocyte migration across the BBB and choroid plexus.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Biochemistry & Molecular Biology
Cristina Municio, Laura Carrero, Desiree Antequera, Eva Carro
Summary: The glymphatic system, responsible for brain waste clearance, is impaired in neurological disorders, including Alzheimer's disease (AD). Understanding the mechanisms and factors controlling glymphatic function, especially involving aquaporins (AQPs), is crucial. CSF transport through the brain parenchyma is important for waste removal, but a balance with CSF production and secretion is necessary. Any disruption in CSF homeostasis affects waste removal and neurodegenerative processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Yi Lu, Carolina Saibro-Girardi, Nicholas Francis Fitz, Mikayla Ranae McGuire, Mary Ann Ostach, A. N. M. Mamun-Or-Rashid, Iliya Lefterov, Radosveta Koldamova
Summary: By analyzing bulk, single-cell, and spatial transcriptomics in APP/PS1 mice exposed to Staphylococcus aureus, we find that chronic peripheral infection leads to transcriptomic changes in the brain, affecting brain barrier function and neuroinflammation. Acute infection also causes specific transcriptional changes related to brain barrier function and neuroinflammation. Additionally, acute infection results in unique transcriptional responses at the amyloid plaque niches, which may facilitate the formation of amyloid plaques and related pathologies. These findings provide important insights into the mechanisms connecting peripheral inflammation to Alzheimer's disease pathology.
Article
Biochemical Research Methods
Vigneshwaran Namasivayam, Katja Stefan, Katja Silbermann, Jens Pahnke, Michael Wiese, Sven Marcel Stefan
Summary: This study successfully extracted molecular structural features of inhibitors of the model protein family of ATP-binding cassette (ABC) transporters using a feature-driven computer-aided pattern analysis (C@PA) method and expanded the known multitarget modulator landscape of pan-ABC transporter inhibitors.
Article
Pharmacology & Pharmacy
Zoe Oesterreicher, Sabine Eberl, Beatrix Wulkersdorfer, Peter Matzneller, Claudia Eder, Esther van Duijn, Wouter H. J. Vaes, Birgit Reiter, Thomas Stimpfl, Walter Jager, Alina Nussbaumer-Proell, Daniela Marhofer, Peter Marhofer, Oliver Langer, Markus Zeitlinger
Summary: This study confirms the feasibility of microdosing for pharmacokinetic measurements in plasma and subcutaneous tissue, and suggests that microdosing combined with microdialysis is a potentially useful tool in clinical antimicrobial drug development. Further studies are needed to assess its applicability for pulmonary pharmacokinetics with bronchoalveolar lavage.
CLINICAL PHARMACOKINETICS
(2022)
Article
Chemistry, Multidisciplinary
Irene Hernandez-Lozano, Severin Mairinger, Thomas Filip, Michael Sauberer, Thomas Wanek, Johann Stanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: The study demonstrates that P-glycoprotein can affect the pulmonary disposition of inhaled drugs, with decreased P-gp activity potentially leading to lower lung exposure and decreased therapeutic efficacy. PET imaging with intratracheally aerosolized radiotracers shows promise for assessing the impact of membrane transporters on pulmonary drug delivery in both rodents and potentially in humans.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Medicine, Research & Experimental
Tal Burt, Ad F. Roffel, Oliver Langer, Kirsten Anderson, Joseph DiMasi
Summary: Research shows that microdosing and phase 0 approaches can accelerate drug development timelines, reduce clinical development attrition, and lower the risk for research volunteers and costs associated with clinical trials.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Solene Marie, Irene Hernandez-Lozano, Marc Le Vee, Louise Breuil, Wadad Saba, Maud Goislard, Sebastien Goutal, Charles Truillet, Oliver Langer, Olivier Fardel, Nicolas Tournier
Summary: Endotoxemia-induced inflammation affects the activity of hepatocyte transporters, leading to changes in drug and bile acid elimination. Tc-99m-mebrofenin imaging is useful for studying disease-related alterations in hepatocyte transporter function.
Article
Biochemistry & Molecular Biology
Michael Woelfl-Duchek, Severin Mairinger, Irene Hernandez-Lozano, Thomas Filip, Viktoria Zoufal, Mathilde Loebsch, Johann Stanek, Claudia Kuntner, Thomas Wanek, Martin Bauer, Jens Pahnke, Oliver Langer
Summary: The effect of thiethylperazine on the transport activity of MRP1 was assessed in this study. Results showed that thiethylperazine treatment had no significant effect on MRP1 activity in the brain and lungs of wild-type and APP/PS1-21 mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Severin Mairinger, Irene Hern, Thomas Filip, Michael Sauberer, Mathilde Lobsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: This study used positron emission tomography (PET) imaging to investigate the influence of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pulmonary distribution of inhaled drugs. The results showed functional activity of P-gp and BCRP in the lungs and suggested that these transporters play a role in limiting the uptake of drugs in the lungs, similar to the blood-brain barrier. The study highlights the importance of pulmonary efflux transporters in the efficacy and safety of inhaled drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Medicinal
Sachin Puri, Katja Stefan, Sharuk L. Khan, Jens Pahnke, Sven Marcel Stefan, Kapil Juvale
Summary: A new MCT1 modulator with potent inhibitory and anticancer activities, selective against MCT4, was discovered. The lead compound also showed significant inhibitory effects against ABCB1 and reversed multidrug resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Severin Mairinger, Irene Hernandez-Lozano, Lena Zachhuber, Thomas Filip, Mathilde Loebsch, Markus Zeitlinger, Marcus Hacker, Carsten Ehrhardt, Oliver Langer
Summary: This study used PET imaging to examine the impact of inhaled glucocorticoid budesonide on pulmonary MRP1 activity in rats. The results showed that inhaled budesonide had no significant effect on pulmonary MRP1 activity.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shiraz Dib, Rodrigo Azevedo Loiola, Emmanuel Sevin, Julien Saint-Pol, Fumitaka Shimizu, Takashi Kanda, Jens Pahnke, Fabien Gosselet
Summary: Neuroinflammation and brain lipid imbalances are observed in individuals with Alzheimer's disease. The tumor necrosis factor-a (TNFa) and liver X receptor (LXR) signaling pathways are involved in both processes, but their relationships in human brain pericytes (HBP) of the neurovascular unit are not well understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pablo Bascunana, Mirjam Brackhan, Luisa Moehle, Jingyun Wu, Thomas Bruening, Ivan Eiriz, Baiba Jansone, Jens Pahnke
Summary: Alzheimer's disease is the most common cause of dementia, and the use of fingolimod as a treatment for Alzheimer's disease is controversial. The effectiveness of fingolimod treatment depends on the stage at which it is administered. In this study, treatment with fingolimod only reduced A beta load in male animals in the late treatment group, while no other treatment groups showed any differences compared to the control group.
Article
Medicine, Research & Experimental
Myriam El Biali, Sylvain Auvity, Salvatore Cisternino, Maria Smirnova, Marcus Hacker, Markus Zeitlinger, Severin Mairinger, Nicolas Tournier, Martin Bauer, Oliver Langer
Summary: PET imaging was used to investigate the effect of P-gp and BCRP inhibition on the distribution of [C-11]erlotinib in the human retina and brain. The results showed that the inhibition of P-gp and BCRP had different effects on the distribution of erlotinib in the retina and brain.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biology
Luisa Moehle, Katja Stefan, Pablo Bascunana, Mirjam Brackhan, Thomas Bruening, Ivan Eiriz, Ahmed El Menuawy, Sylvie van Genderen, Irene Santos-Garcia, Anna Maria Gorska, Maria Villa, Jingyun Wu, Sven Marcel Stefan, Jens Pahnke
Summary: Reusing drugs may accelerate the development of effective dementia treatment. However, the drug dimethyl fumarate was found to be inefficient in reducing Alzheimer's disease-related changes in the brain due to the involvement of an essential brain transporter.
Article
Chemistry, Medicinal
Sachin Puri, Katja Stefan, Sharuk L. Khan, Jens Pahnke, Sven Marcel Stefan, Kapil Juvale
Summary: Researchers synthesized a library of indole-based compounds and discovered that one of these compounds (compound 24) has potential for cancer treatment. This compound inhibits MCT1, prevents cancer cell proliferation, induces apoptosis, and has the ability to reverse multidrug resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Johanne U. Hermansen, Dorota M. Wojcik, Nina Robinson, Jens Pahnke, Hans Kristian Haugland, Ann Helen Jamtoy, Trond Flaegstad, Hanne Halvorsen, Bendik Lund, Lars O. Baumbusch, Monica C. Munthe-Kaas
Summary: This study aimed to establish a prospective and centralized biobank for infants, children, and adolescents diagnosed with cancer in Norway. With judicial and ethical approvals obtained through a consortium, steering committee, and advisory board, pipelines including SOPs for all aspects of the biobank process were developed. By January 1, 2021, approximately 12,000 samples from 510 patients had been included, with a 96% consent and participation rate among newly diagnosed patients.
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)