Article
Multidisciplinary Sciences
Geok-Lin Chua, Bryan C. Tan, Randy Y. J. Loke, Menglan He, Cheen-Fei Chin, Bernice H. Wong, Alvin C. Y. Kuk, Mei Ding, Markus R. Wenk, Lan Guan, Federico Torta, David L. Silver
Summary: Mfsd2a is a sodium-dependent lysophosphatidylcholine transporter expressed at the blood-brain barrier that is crucial for omega-3 fatty acid transport and brain development. Although the transport mechanism of Mfsd2a has been proposed through cryo-EM structures, the biochem-ical evidence of flippase activity and sodium-dependent LPC inversion is still lacking. In this study, an in vitro assay using recombinant Mfsd2a reconstituted in liposomes was established to demonstrate the flipping of lysophosphatidylserine (LPS) from the outer to the inner leaflet of a membrane bilayer in a sodium-dependent manner. Through cryo-EM structures, mutagenesis, and cell-based transport assay, amino acid residues important for Mfsd2a activity were identified, providing direct biochemical evidence of Mfsd2a functioning as a lysolipid flippase.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Engineering, Biomedical
Xiufeng Ju, Tongtong Miao, Haiyan Chen, Jiang Ni, Liang Han
Summary: Mfsd2a plays a crucial role in regulating the transcytosis and permeability of the blood-brain barrier. Strategies involving priming nanoparticles and drug-loaded nanoparticles have shown promising results in enhancing BBB crossing efficiency and brain accumulation of therapeutics for breast cancer brain metastases.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Cell Biology
Hideto Osada, Eriko Toda, Kohei Homma, Naymel A. Guzman, Norihiro Nagai, Mamoru Ogawa, Kazuno Negishi, Makoto Arita, Kazuo Tsubota, Yoko Ozawa
Summary: Mutations in lipid metabolism-related genes may lead to retinal degeneration, as evidenced by Adipor1 knockout mouse models showing neurodegeneration and visual dysfunction. Adipor1 deficiency is crucial for proper photoreceptor function and survival, likely through mechanisms involving Elovl2 repression and increased expression of lipogenic genes.
CELL DEATH & DISEASE
(2021)
Article
Pharmacology & Pharmacy
Alice Brookes, Adelaide Jewell, Wanshan Feng, Tracey D. Bradshaw, James Butler, Pavel Gershkovich
Summary: This study investigated the delivery of cannabidiol (CBD) to the brain following oral administration in lipid-based and lipid-free vehicles. It was observed that different formulations resulted in different CBD delivery to the whole brain and various brain regions, indicating the importance of oral formulation selection for optimal delivery to specific brain regions.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Oncology
Brett R. Loman, Kathryn L. G. Russart, Corena Grant, Alexis J. Lynch, Michael T. Bailey, Leah M. Pyter
Summary: This study examines the effects of orthotopic mammary tumor implantation, growth, and resection on fecal bacteriome composition and intestinal barrier function in relation to systemic inflammation and enteric bacterial translocation in mice. The results indicate that mammary tumors can alter the microbiome, reduce intestinal barrier function, increase translocation of enteric bacteria, and induce systemic inflammation.
Article
Physiology
Somasundaram Raghavan, Masuma Akter Brishti, Daniel Mohr Collier, M. Dennis Leo
Summary: Blood-brain-barrier permeability is regulated by endothelial junctional proteins. P2Y1R signaling pathway leads to the downregulation of endothelial barrier function. Following hypoxia and reoxygenation, P2Y1R expression is upregulated, endothelial junctional markers are downregulated, and endothelial permeability increases.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Oncology
Edgar Petrosyan, Jawad Fares, Alex Cordero, Aida Rashidi, Victor A. Arrieta, Deepak Kanojia, Maciej S. Lesniak
Summary: Malignant brain tumors, such as glioblastoma multiforme (GBM) and brain metastases, pose a major medical challenge due to the blood-brain barrier (BBB) preventing the effectiveness of most treatment options. This study explores the potential of repurposing BBB-permeable antidepressants as a promising option for treating brain tumors. The research provides an overview of FDA-approved antidepressants and their cytotoxic activities in different tumor models, with a focus on the role of autophagy dysregulation.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Nanoscience & Nanotechnology
Cong Yang, Mengmeng Han, Ruoyu Li, Ligui Zhou, Ying Zhang, Lining Duan, Shiyu Su, Min Li, Qi Wang, Tongkai Chen, Yousheng Mo
Summary: Intracerebral hemorrhage (ICH) is a severe form of stroke with pathology related to ferroptosis, a type of programmed cell death. Curcumin (Cur) has therapeutic potential for ICH but faces challenges due to poor solubility and bioavailability. Encapsulating Cur in nanoparticles (Cur-NPs) improves its delivery to the brain and shows promising therapeutic effects in treating ICH, including suppressing ferroptosis.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Yang-Bao Miao, Kuan-Hung Chen, Chiung-Tong Chen, Fwu-Long Mi, Yu-Jung Lin, Yen Chang, Chi-Shiun Chiang, Jui-To Wang, Kun-Ju Lin, Hsing-Wen Sung
Summary: An oral prodrug delivery system has been developed to target gliomas by overcoming the intestinal epithelial barrier and the blood-brain barrier. The prodrug specifically targets intestinal M cells, crosses the barriers, and releases the active drug at the tumor site for improved therapeutic efficacy.
ADVANCED MATERIALS
(2021)
Article
Medicine, Research & Experimental
Cheen Fei Chin, Dwight L. A. Galam, Liang Gao, Bryan C. Tan, Bernice H. Wong, Geok-Lin Chua, Randy Y. J. Loke, Yen Ching Lim, Markus R. Wenk, Miao-Shan Lim, Wei-Qiang Leow, George B. B. Goh, Federico Torta, David L. Silver
Summary: This study reveals the critical role of the lysophosphatidylcholine transporter Mfsd2a in maintaining hepatic phospholipid pools. Deficiency of Mfsd2a leads to a NASH-like phenotype and reduced hepatic phospholipids. LPCs containing polyunsaturated fatty acids promote hepatic lipid droplet formation and suppress lipogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Maria Martinez-Molledo, Emmanuel Nji, Nicolas Reyes
Summary: This study reports the structure of the human MFSD2A-SYNC2 complex and reveals its importance in brain and placenta development and function. Additionally, SYNC2 acts as an inhibitor of MFSD2A transport, providing a new strategy for delivering therapeutic macromolecules across the blood-brain barrier.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Alice Brookes, Liuhang Ji, Tracey D. Bradshaw, Michael Stocks, David Gray, James Butler, Pavel Gershkovich
Summary: This review explores the feasibility of oral lipid-based drug delivery to the brain and discusses various lipids that can potentially be delivered orally. Current data suggests that oral administration can increase the permeability of the blood-brain barrier (BBB), and further research is needed to investigate the use of lipid-based drug delivery for brain targeting.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Yen T. K. Nguyen, Hoa T. T. Ha, Tra H. Nguyen, Long N. Nguyen
Summary: The brain exchanges nutrients and small molecules with blood through the blood-brain barrier, and glucose plays a critical role in providing energy for the brain. The brain also takes up various substances through different transport systems, and unraveling these mechanisms is key in understanding the brain's nutritional requirements and potential therapeutic interventions for neurological disorders.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Erica A. Power, Julian S. Rechberger, Sumit Gupta, Jonathan D. Schwartz, David J. Daniels, Soumen Khatua
Summary: Although there has been a surge in the identification of molecular targets and targeted therapies in pediatric brain tumors in the last decade, the blood brain barrier (BBB) remains a significant challenge for systemic drug delivery. Recent efforts have identified strategies to enhance drug delivery into pediatric brain tumors, including invasive and non-invasive technologies.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Scott Schoen, M. Sait Kilinc, Hohyun Lee, Yutong Guo, F. Levent Degertekin, Graeme F. Woodworth, Costas Arvanitis
Summary: Brain tumors located in the central nervous system (CNS) present a unique challenge due to limited drug access to the brain tumor microenvironment (TME). Recent advancements in microbubble ultrasound contrast agents and ultrasound energy have shown promise in enhancing drug delivery to brain tumors. This technology has the potential to improve the effectiveness of both traditional chemotherapy and novel immunotherapeutic agents. Early clinical studies have demonstrated safety, and ongoing Phase I/II trials are testing the preclinical findings.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Multidisciplinary Sciences
Shweta Tiwary, Lei Xu
Correction
Multidisciplinary Sciences
Shweta Tiwary, Lei Xu
Article
Oncology
S. Tiwary, M. Preziosi, P. G. Rothberg, N. Zeitouni, N. Corson, L. Xu
Article
Oncology
Anja C. Bloom, Lewis H. Bender, Shweta Tiwary, Lise Pasquet, Katharine Clark, Tianbo Jiang, Zheng Xia, Aizea Morales-Kastresana, Jennifer C. Jones, Ian Walters, Masaki Terabe, Jay A. Berzofsky
Review
Immunology
Shweta Tiwary, Jay A. Berzofsky, Masaki Terabe
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Oncology
Guoqiang Chang, Lei Shi, Youqiong Ye, Hailing Shi, Lixian Zeng, Shweta Tiwary, Jason T. Huse, Lei Huo, Li Ma, Yongjie Ma, Sicong Zhang, Jianwei Zhu, Victoria Xie, Peng Li, Leng Han, Chuan He, Suyun Huang
Meeting Abstract
Dermatology
S. Tiwary, M. Preziosi, S. Mohanti, B. Martin, N. Zeitouni, L. Xu
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2013)