Article
Endocrinology & Metabolism
Nicolas Tournier, Sebastien Goutal, Severin Mairinger, Irene Hernandez-Lozano, Thomas Filip, Michael Sauberer, Fabien Caille, Louise Breuil, Johann Stanek, Anna F. Freeman, Gaia Novarino, Charles Truillet, Thomas Wanek, Oliver Langer
Summary: This study investigated the feasibility of simultaneous inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar. The combination led to increased brain distribution of the model substrate in mice and macaques, potentially enhancing brain delivery of molecularly targeted anticancer drugs for the treatment of brain tumors. Additionally, tolerability and induction of apoptosis were assessed in human cerebral organoids, showing promising results for future applications.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Hironobu Yagishita, Hideaki Kagaya, Mitsuru Saito, Kazuyuki Numakura, Ryohei Yamamoto, Ryuichiro Sagehashi, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
Summary: The study evaluated the effects of NR1I2 and ABCB1 genetic polymorphisms on everolimus pharmacokinetics in Japanese renal transplant patients. The results showed significant correlations between different genotypes, gender, age, and liver function with the dose-adjusted AUC(0-12) of everolimus. Therefore, age and liver function should be considered when evaluating dose reductions for everolimus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yu Siong Ho, Pablo Torres-Vergara, Jeffrey Penny
Summary: This study investigated the effects of NR3C1, NR1I3, NR1I2 and NR2B1 activation on porcine brain endothelial cells (PBECs). The results showed that NR1I2 agonist Rifampicin up-regulated ABCG2 activity, while NR1I2 antagonist L-sulforaphane counteracted this effect. NR1I3 agonist and inverse agonist down-regulated ABCB1, ABCG2 and ABCC5 activity. NR3C1 agonist increased ABCB1, ABCG2 and ABCC5 activity and protein expression, which was counteracted by NR3C1 antagonist. NR1I3 and NR3C1 were found to regulate ABCC5 activity and protein expression in BBB endothelial cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ondrej Martinec, Carin Biel, Inge A. M. de Graaf, Martin Huliciak, Koert P. de Jong, Frantisek Staud, Filip Cecka, Peter Olinga, Ivan Vokral, Lukas Cerveny
Summary: This study utilized human precision-cut intestinal slices (hPCISs) to investigate the induction of functional expression of ABCB1 by rifampicin. Results demonstrated that rifampicin significantly increased gene expression, protein levels, and efflux activity of ABCB1 in hPCISs, suggesting the potential value of hPCISs in evaluating drugs' ABCB1-inducing potency in the human intestine.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Kerri Devine, Elisa Villalobos, Catriona J. Kyle, Ruth Andrew, Rebecca M. Reynolds, Roland H. Stimson, Mark Nixon, Brian R. Walker
Summary: The regulation of hormone responses involves modulating hormone concentrations in both circulation and target tissues. While the role of enzymes and transmembrane transporters in regulating glucocorticoid and thyroid hormone responses is well-established, their roles in steroid hormone responses have been less explored. Recent studies suggest that ABCB1 and ABCC1 transporters play a critical role in differential transport of exogenous and endogenous glucocorticoids, leading to tissue-specific sensitivity to different steroids. This review summarizes the evidence and new insights into the physiology and pharmacology of glucocorticoid action, including novel approaches to glucocorticoid replacement.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Robert W. Robey, Andrea N. Robinson, Fatima Ali-Rahmani, Lyn M. Huff, Sabrina Lusvarghi, Shahrooz Vahedi, Jordan M. Hotz, Andrew C. Warner, Donna Butcher, Jennifer Matta, Elijah F. Edmondson, Tobie D. Lee, Jacob S. Roth, Olivia W. Lee, Min Shen, Kandice Tanner, Matthew D. Hall, Suresh Ambudkar, Michael M. Gottesman
Summary: This research investigated two genes, abcb4 and abcb5, similar to ABCB1 in the zebrafish BBB, unveiling differences in substrate resistance between Abcb4 and Abcb5. Abcb4 demonstrated overlapping substrate specificity with P-gp, suggesting its functional resemblance to P-gp, making zebrafish a potential model for studying P-gp at the BBB.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Simona Sucha, Ales Sorf, Martin Svoren, Dimitrios Vagiannis, Fahda Ahmed, Benjamin Visek, Martina Ceckova
Summary: This study evaluated the clinical relevance of ABCB1 in AML patients and found that overexpression of ABCB1 was associated with adverse prognosis. Midostaurin, as an ABCB1 inhibitor, increased the accumulation of anthracyclines in AML patients and promoted apoptosis in leukemic cells. Additionally, miR-9 was identified as a useful prognostic marker in AML.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Multidisciplinary Sciences
Iman Imtiyaz Ahmed Juvale, Azzmer Azzar Abdul Hamid, Khairul Bariyyah Abd Halim, Ahmad Tarmizi Che Has
Summary: The multidrug resistance phenomenon poses a significant threat to the pharmaceutical industry and is mediated by multidrug transporters like P-glycoprotein. P-glycoprotein, with its versatile binding sites, accommodates various compounds and plays crucial roles in both multidrug resistant diseases and physiological functions in the human body.
Article
Chemistry, Multidisciplinary
Jelena Vasiljeva, Marina Makrecka-Kuka, Ilona Domracheva, Karlis Vilks, Pavels Dimitrijevs, Pavel Arsenyan
Summary: This study reports the design and synthesis of novel selenophenoquinolinones and their ability to reverse doxorubicin resistance in uterus sarcoma cells. Compound 5e demonstrated the best cytotoxicity and attenuated cell resistance to doxorubicin by inhibiting ABCB1 transporter activity and suppressing ABCB1 gene expression.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hinako Nagano, Seiryo Ogata, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki
Summary: This study reveals the role of Podocalyxin (PODXL) in blood-brain barrier function. PODXL knockdown affects immune response and intracellular trafficking, and regulates the protein expression and efflux activity of ABCB1/MDR1.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Jinyun Dong, Li Yuan, Can Hu, Xiangdong Cheng, Jiang -Jiang Qin
Summary: Multidrug resistance (MDR) is a major threat in chemotherapy, and the overexpression of ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (P-gp)/ABCB1, plays a role in MDR. Targeting P-gp with small molecule inhibitors is an effective approach, but no clinically useful inhibitors have been identified so far. Therefore, further research is needed to overcome MDR.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Liadys Mora Lagares, Yunierkis Perez-Castillo, Nikola Minovski, Marjana Novic
Summary: P-gp is an important protein involved in drug efflux and multidrug resistance. Molecular dynamics simulations can provide valuable insights into the binding behavior and conformational changes of P-gp in the presence of different compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Hematology
Lin Zhang, Irina Graf, Yaoyun Kuang, Xuan Zheng, Matteo Haupt, Arshad Majid, Ertugrul Kilic, Dirk M. Hermann, Marios-Nikos Psychogios, Martin S. Weber, Jasmin Ochs, Mathias Baehr, Thorsten R. Doeppner
Summary: The study found that EVs derived from neural progenitor cells enhance poststroke BBB integrity via regulation of ABCB1 and MMP-9, attenuating inflammatory cell recruitment by inhibiting the NF-kappa B pathway.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Neurosciences
Xiaomei Lin, Tianyuyi Feng, Erheng Cui, Yunfei Li, Zhang Qin, Xiaohu Zhao
Summary: This study successfully established a rat model based on the genetic-environmental interaction, which exhibited phenotype characteristics similar to human AD in terms of cognitive function, brain microstructure, and immunohistochemistry. The genetic factor (APP mutation) and the environmental factor (acrolein exposure) accounted for 39.74% and 33.3% of the AD-like phenotypes in the model, respectively.
Article
Neurosciences
Gustavo Guimara Guerrero, Giovanna Bignoto Minhoto, Camilla dos Santos Tiburcio-Machado, Itza Amarisis Ribeiro Pinto, Claudio Antonio Federico, Marcia Carneiro Valera
Summary: The present study evaluated the influence of head and neck radiotherapy on the behavior and body weight gain in Wistar rats. The results demonstrated that different doses of radiation induced depressive behavior in the animals, and that the weight gain tended to be lower in the irradiated groups.
Article
Neurosciences
Ziwei Gao, Chao Lu, Yaping Zhu, Yuxin Liu, Yuesong Lin, Wenming Gao, Liyuan Tian, Lei Wu
Summary: This study reveals the underlying mechanisms of the rapid antidepressant effects of merazin hydrate (MH), which activates CaMKII to promote neuronal activities and proliferation in the hippocampus.
Article
Neurosciences
Kathleen E. Murray, Whitney A. Ratliff, Vedad Delic, Bruce A. Citron
Summary: Gulf War Illness (GWI) is a chronic disorder that affects approximately 30% of Veterans deployed to the Persian Gulf. This study found that exposure to toxicants during the Gulf War resulted in long-term changes in the morphology of dentate granule cells and that treatment with Nrf2 activator could improve neuronal health in the hippocampus.
Article
Neurosciences
Jing Li, Yan Zou, Xiangchuang Kong, Yangming Leng, Fan Yang, Guofeng Zhou, Bo Liu, Wenliang Fan
Summary: This study examines the functional connectivity changes in individuals with sudden sensorineural hearing loss (SSNHL) at the integrity, network, and edge levels. The findings reveal reduced intranetwork connectivity strength and increased internetwork connectivity in SSNHL patients. These alterations are associated with the duration of SSNHL and Tinnitus Handicap Inventory scores. The study provides crucial insights into the neural mechanisms of SSNHL and the brain's network-level responses to sensory loss.
Review
Neurosciences
Didier Majou, Anne-Lise Dermenghem
Summary: In the early stages of SAD, memory impairment is strongly correlated with cortical levels of soluble amyloid-beta peptide oligomers. A beta disrupts glutamatergic synaptic function and leads to cognitive deficits. This article describes the pathogenic mechanisms underlying cerebral amyloidosis, involving amyloid precursor protein synthesis, A beta residue clearance processes, and the role of specific molecules.
Article
Neurosciences
Jing Li, Yi Shan, Xiaojing Zhao, Guixiang Shan, Peng-Hu Wei, Lin Liu, Changming Wang, Hang Wu, Weiqun Song, Yi Tang, Guo-Guang Zhao, Jie Lu
Summary: This study investigates changes in brain anatomical structures and functional network connectivity after chronic complete thoracic spinal cord injury (cctSCI) and their impact on clinical outcomes. The findings reveal alterations in gray matter volume and functional connectivity in specific brain regions, indicating potential therapeutic targets and methods for tracking treatment outcomes.
Article
Neurosciences
Anllely Fernandez, Katherine Corvalan, Octavia Santis, Maxs Mendez-Ruette, Ariel Caviedes, Matias Pizarro, Maria -Teresa Gomez, Luis Federico Batiz, Peter Landgraf, Thilo Kahne, Alejandro Rojas-Fernandez, Ursula Wyneken
Summary: This study reveals the importance of SUMOylation in modulating the protein cargo of astrocyte-derived small extracellular vesicles (sEVs) and its potential impact on neurons.
Article
Neurosciences
Anika Luettig, Stefanie Perl, Maria Zetsche, Franziska Richter, Denise Franz, Marco Heerdegen, Ruediger Koehling, Angelika Richter
Summary: This study found that changes in c-Fos activity during short-term stimulation of the entopeduncular nucleus (EPN) are associated with improvement in dystonia, and also discovered that the cerebellum may be involved in the antidystonic effects.
Article
Neurosciences
Yanlin Tao, Wei Shen, Houyuan Zhou, Zikang Li, Ting Pi, Hui Wu, Hailian Shi, Fei Huang, Xiaojun Wu
Summary: Depression has a higher incidence in women compared to men, and this study investigated the impact of sex on depressive behaviors and underlying mechanisms using a corticosterone-induced depression model in mice. The results showed sex-specific anxiety and depression behaviors in the model group, as well as differences in protein expression and neurotransmitter levels between male and female mice. These findings enhance our understanding of sex-specific differences in depression and support tailored interventions.
Review
Neurosciences
Dnyandev G. Gadhave, Vrashabh V. Sugandhi, Chandrakant R. Kokare
Summary: This article discusses the characteristics and importance of the tight junctions of endothelial cells in the CNS, which act as a biological barrier known as the blood-brain barrier (BBB). It focuses on overcoming the challenges of delivering therapeutic agents to the brain in neurodegenerative disorders, particularly multiple sclerosis, through the use of biomaterials. The article also highlights the current limitations of animal models for studying multiple sclerosis and suggests a potential future research direction.
Article
Neurosciences
Li-Min Mao, Khyathi Thallapureddy, John Q. Wang
Summary: Propofol can enhance synapsin phosphorylation and modulate synaptic transmission in the mouse brain. The study reveals the potential role of synapsin as a substrate of propofol and its effects on neurotransmitter release machinery.
Article
Neurosciences
Syed Maaz Ahmed Rizvi, Abdul Baseer Buriro, Irfan Ahmed, Abdul Aziz Memon
Summary: This study explores the effects of prolonged mask usage on the human brain by analyzing EEG and physiological parameters. The results show that the mean EEG spectral power in alpha, beta, and gamma sub-bands of individuals wearing masks is smaller than those without masks. The performances on cognitive tasks and oxygen saturation level differ between the two groups, while blood pressure, body temperature, and heart rate are similar. The analysis also reveals that the occipital and frontal lobes exhibit the greatest variability in channel measurements.
Article
Neurosciences
Rui-Fang Ma, Lu-Lu Xue, Jin-Xiang Liu, Li Chen, Liu-Lin Xiong, Ting-Hua Wang, Fei Liu
Summary: This study observed changes in brain infarction and blood vessels in rats during neonatal hypoxic ischemic encephalopathy (NHIE) modeling using Transcranial Doppler Ultrasonography (TCD). Longer duration of hypoxia was associated with more severe nerve damage. TCD can dynamically monitor cerebral infarction after NHIE modeling, which may serve as a useful auxiliary method for evaluating animal experimental models.
Article
Neurosciences
Yuxiang Dai, Chen Yu, Lu Zhou, Longyang Cheng, Hongbin Ni, Weibang Liang
Summary: Overexpression of CXCR4 in glioma is correlated with patient survival, and its inhibition can reduce invasion and migration of glioma cells. Inhibiting Nur77 also decreases cancer progression associated with CXCR4.