Article
Chemistry, Multidisciplinary
Yanrong Su, Yufen Huang, Qinjie Kou, Lu Lu, Haiye Jiang, Xisheng Li, Rong Gui, Rong Huang, Xueyuan Huang, Jinqi Ma, Jian Li, Xinmin Nie
Summary: In this study, a biomimetic delivery nanosystem TR-ZRA was developed to improve the immune environment of Alzheimer's disease (AD) by targeting the blood-brain barrier. TR-ZRA loaded with CD22shRNA plasmid silenced the abnormally high expression molecule CD22 in aging microglia, enhancing their ability to phagocytose A beta and alleviate complement activation. TR-ZRA also enabled rapid and low-cost monitoring of A beta plaques. After treatment, learning and memory abilities were improved in AD mice. Overall, TR-ZRA provides a promising strategy and novel immune targets for AD therapy.
Article
Multidisciplinary Sciences
Shuyan Yang, Shanhu Cao, Xuebing Xu, Quan Li, Jianting Li, Jin Guo, Fang Wang, Yihua Bao, Zean Jiang, Ting Zhang, Li Wang, Shaoguang Sun
Summary: In this study, the researchers generated add1-deficient zebrafish models and found that Add1 plays a crucial role in hematopoiesis, specifically in erythrocyte development. Lack of Add1 resulted in impaired primitive and definitive hematopoiesis, as well as activation of the p53 pathway leading to apoptosis. Partial rescue of the phenotype was observed when p53 was insufficient, indicating the involvement of the p53-mediated apoptotic pathway. Mechanistically, ADD1 was found to regulate promoter activity, expanding its regulatory role beyond cytoskeletal functions.
Article
Biophysics
Insu Kim, Yonghwan Kim, Sang Won Lee, Dongtak Lee, Hyo Gi Jung, Jae Won Jang, Taeha Lee, Young Kyung Yoon, Gyudo Lee, Dae Sung Yoon
Summary: In this study, erythrocyte-camouflaged biosensors (ECB) were fabricated for sensitive detection of Staphylococcus aureus-secreted alpha-hemolysin (Hla) using erythrocyte membrane (EM) extracted from human whole blood as a novel bioreceptor. The ECB showed higher sensitivity to Hla compared to major blood proteins, with signal intensities 8.8-12.7 times higher than those of the same concentration of blood proteins. Additionally, the ECB exhibited a detection limit of 1.9 ng/ml for Hla with a dynamic range of 0.0001-1 mg/ml and maintained constant sensing performance with 99.0 +/- 5.6% accuracy during 35 days of storage.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Biochemistry & Molecular Biology
Arit Ghosh, Megan Coffin, Richard West, Velia M. Fowler
Summary: Tmod3 plays a crucial role in erythroid differentiation by nucleating F-actin assembly and promoting the incorporation of Tmod1 and Tpms into the membrane skeleton, which is essential for morphological maturation and cell survival.
Article
Biochemistry & Molecular Biology
Nghi M. Nguyen, Neetha N. Vellichirammal, Chittibabu Guda, Gurudutt Pendyala
Summary: This study investigates the potential impact of long-term exposure to midazolam (MDZ), a common benzodiazepine used as a sedative in the neonatal intensive care unit (NICU), on synaptic function. The results suggest that both short-term and long-term exposure to MDZ can lead to learning disturbances and perturb neurobehavioral outcomes at later stages of life.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fu-Long Li, Vivian Fu, Guangbo Liu, Tracy Tang, Andrei W. Konradi, Xiao Peng, Esther Kemper, Benjamin F. Cravatt, J. Matthew Franklin, Zhengming Wu, Joshua Mayfield, Jack E. Dixon, William H. Gerwick, Kun-Liang Guan
Summary: The Hippo pathway is crucial for development, organ size control, and tissue homeostasis, and its dysregulation is linked to cancer. In this study, a marine natural product called microcolin B (MCB) was identified as a Hippo activator that selectively kills YAP-dependent cancer cells. Structural optimization led to the discovery that phosphatidylinositol transfer proteins alpha and beta (PITP alpha/beta) are the direct molecular targets of MCB. The study reveals a previously unknown role of PITP alpha/beta in regulating the Hippo pathway and suggests them as potential therapeutic targets for cancer.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Vera B. Dugina, Galina S. Shagieva, Anton S. Shakhov, Irina B. Alieva
Summary: Endothelial cells (EC) line the inner surface of vessels and regulate vascular permeability, with their actin cytoskeleton crucial for maintaining endothelial barrier function. Non-muscle cells express two actin isoforms, beta and gamma, which have different roles in cell survival, cell division, and neoplastic transformation depending on the cell type. The spatial organization of cytoplasmic actins in different cell types, particularly in endothelial cells, is closely linked to their functional activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Astronomy & Astrophysics
Fabiana De Cesare, Lorenzo Di Pietro, Marco Serone
Summary: In this study, UV fixed points of non-Abelian SU(n(c)) gauge theories in 4 + 2 epsilon dimensions with n(f) Dirac fermions in the fundamental representation were sought using five-loop beta-function and resummation techniques. Evidence for a five-dimensional UV fixed point for SU(2) theories with n(f) <= 4 and pure SU(n(c)) theories for n(c) <= 4 was found. Anomalous dimensions and operator calculations were also performed at the UV fixed point.
Article
Physics, Multidisciplinary
Saralees Nadarajah, Malick Kebe
Summary: Entropies are useful measures of variation, but explicit expressions for entropies are limited in the literature. This paper provides a comprehensive collection of explicit expressions for four common entropies in over sixty continuous univariate distributions. Most of the derived expressions are new and involve known special functions.
Article
Multidisciplinary Sciences
Maria E. Falzone, Roderick MacKinnon
Summary: Phospholipase C-beta s (PLC beta s) catalyze the hydrolysis of phosphatidylinositol 4, 5-bisphosphate (PIP2) into inositoltriphosphate (IP3) and diacylglycerol (DAG). PIP2 regulates the activity of many membrane proteins, while IP3 and DAG lead to increased intracellular Ca2+ levels and activate protein kinase C, respectively. PLC beta s are regulated by G protein-coupled receptors through direct interaction with G alpha(q) and G beta gamma and are aqueous-soluble enzymes that must bind to the cell membrane to act on their lipid substrate.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Mingxi Li, Liang Wang, Dalin Tang, Gutian Zhao, Zhonghua Ni, Ning Gu, Fang Yang
Summary: Platelet membrane biomimetic nanobubbles (PNBs) with ideal echogenicity were fabricated using an adjustable pressure-induced shear stress method, enriching platelet membrane lipid rafts and proteins during high shear stress. The conformation of platelet integrin alpha(IIb)beta(3) was transformed into a shear stress-induced intermediate affinity state, enhancing PNBs' adhesion ability to vascular endothelial injury for potential targeted ultrasound diagnosis.
Article
Neurosciences
Min Xiong, Li Zou, Lanxia Meng, Xingyu Zhang, Ye Tian, Guoxin Zhang, Jiaolong Yang, Guiqin Chen, Jing Xiong, Keqiang Ye, Zhentao Zhang
Summary: The study reveals that AEP-mediated fragmentation of gamma-adducin plays a crucial role in Alzheimer's disease. Blocking the activity of AEP might offer a novel therapeutic target for AD.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pablo Zambrano, Mario Suwalsky, Malgorzata Jemiola-Rzeminska, Maria Jose Gallardo-Nelson, Kazimierz Strzalka, Diego Munoz-Torrero
Summary: The study demonstrates the protective effect of AVCRI104P4 against the toxicity induced by A beta(1-42) peptide in human erythrocytes and molecular models. The compound also has a significant impact on the transparency and morphology of human erythrocyte membranes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Jennifer C. Erasmus, Kasia Smolarczyk, Helena Brezovjakova, Noor F. Mohd-Naim, Encarnacion Lozano, Karl Matter, Vania M. M. Braga
Summary: Rac1 GTPase is hyperactivated in tumors and leads to internalization of E-cadherin via micropinocytosis in a PAK1-dependent manner. PAK1 regulates E-cadherin transport by phosphorylating RabGDI beta, which in turn affects Rab retrieval from membranes. This crosstalk between small GTPases impacts Rac1 and PAK1 regulation of membrane remodeling during epithelial dedifferentiation, adhesion, and motility.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Deborah Simao Souza, Carla Macheroni, Gustavo Jose Silva Pereira, Carolina Meloni Vicente, Catarina Segreti Porto
Summary: Prostate cancer is the most common cancer among men worldwide, and hormone-related factors, such as androgens, estrogens, and their receptors, play a crucial role in its development and progression. Galectin-3, a family of proteins, is involved in various stages of tumor development and progression, but its expression regulation is still poorly understood. This review focuses on the interplay between Galectin-3 and estrogen receptor signaling pathways in prostate cancer cells and proposes a molecular mechanism involving ER, Galectin-3, and beta-catenin in the modulation of nuclear transcriptional events. Further understanding of the role of Galectin-3 and ER in prostate cancer could lead to the discovery of new drug targets to treat castration-resistant prostate cancer.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemical Research Methods
Hanwen Zhang, Ananda Kumar Kanduluru, Pooja Desai, Afruja Ahad, Sean Carlin, Nidhi Tandon, Wolfgang A. Weber, Philip S. Low
BIOCONJUGATE CHEMISTRY
(2018)
Article
Biochemical Research Methods
Loganathan Rangasamy, Venkatesh Chelvam, Ananda Kumar Kanduluru, Madduri Srinivasarao, N. Achini Bandara, Fei You, Esteban A. Orellana, Andrea L. Kasinski, Philip S. Low
BIOCONJUGATE CHEMISTRY
(2018)
Article
Biochemical Research Methods
Jyoti Roy, Miranda Kaake, Madduri Sriniyasarao, Philip S. Low
BIOCONJUGATE CHEMISTRY
(2018)
Article
Medicine, Research & Experimental
Isaac S. Marks, Spencer S. Gardeen, Sarah J. Kurdziel, Sonia T. Nicolaou, J. Evan Woods, Sumith A. Kularatne, Philip S. Low
MOLECULAR PHARMACEUTICS
(2018)
Article
Chemistry, Medicinal
Mohamed S. A. Elsayed, Jeffery J. Nielsen, Sungtae Park, Jeongho Park, Qingyang Liu, Chang H. Kim, Yves Pommier, Keli Agama, Philip S. Low, Mark Cushman
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Multidisciplinary
Jeffery J. Nielsen, Stewart A. Low, Neal T. Ramseier, Rahul Hadap, Nicholas A. Young, Mingding Wang, Philip S. Low
Summary: The study aimed to improve bone fracture management by continuously applying bone anabolic agents to the fracture surface. Short oligopeptides of acidic amino acids were found to significantly increase localization of peptide payload to bone fractures, offering a promising strategy for enhancing fracture healing.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Ioannis Tsamesidis, Karine Reybier, Giuseppe Marchetti, Maria Carmina Pau, Patrizia Virdis, Claudio Fozza, Francoise Nepveu, Philip S. Low, Francesco Michelangelo Turrini, Antonella Pantaleo
Article
Biochemical Research Methods
Xin Liu, Weichuan Luo, Boning Zhang, Yong Gu Lee, Imrul Shahriar, Madduri Srinivasarao, Philip S. Low
Summary: In this study, a modified influenza virus neuraminidase inhibitor, zanamivir, was utilized for diagnostic, imaging, and therapeutic purposes in influenza virus infections. Different conjugates like the zanamivir-conjugated rhodamine dye and zanamivir99 mTc radioimaging conjugate were designed for visual monitoring of virus-infected cells. Moreover, targeted cytotoxic drugs and CAR T cells were developed specifically for viral neuraminidase-expressing cells, showing potential for improved treatment of influenza virus infections.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sakkarapalayam M. Mahalingam, Karson S. Putt, Madduri Srinivasarao, Philip S. Low
Summary: The inadvertent severing of a ureter during colorectal surgeries is a common issue, leading to the development of new near-infrared dyes to help surgeons identify ureter location. The new PEGylated UreterGlow derivatives show promising optical and biodistribution characteristics, making them good candidates for translation into the clinic.
Article
Chemistry, Multidisciplinary
John Victor Napoleon, Boning Zhang, Qian Luo, Madduri Srinivasarao, Philip S. Low
Summary: Administering a CAR-targeted TLR7 agonist can reverse CAR T cell exhaustion and successfully treat solid tumors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Oncology
Qian Luo, John Napoleon, Xin Liu, Boning Zhang, Suilan Zheng, Philip S. Low
Summary: This study describes a strategy to reverse CAR T-cell exhaustion by using a universal anti-fluorescein CAR that engages multiple cancer cell clones and acts as a drug-internalizing receptor. By attaching a Toll-like receptor 7 agonist to the anti-fluorescein CAR, they downregulate exhaustion markers and reactivate exhausted CAR-T cells, leading to regression of solid tumors.
MOLECULAR CANCER RESEARCH
(2022)
Article
Engineering, Biomedical
Yun Chang, Gyuhyung Jin, Weichuan Luo, Qian Luo, Juhyung Jung, Sydney N. Hummel, Sandra Torregrosa-Allen, Bennett D. Elzey, Philip S. Low, Xiaojun Lance Lian, Xiaoping Bao
Summary: Adoptive CAR-engineered NK cells have potential for cancer treatment, but limited immunological memory and donor cell availability hinder their applications. We evaluated different CAR constructs to enhance NK cell proliferation and anti-tumor cytotoxicity. We genetically engineered hPSCs with optimized CARs and differentiated them into dual CAR-NK cells. The memory-like hPSC-NK cells showed enhanced anti-tumor activity through antigen-dependent activation of signaling pathways. Our modular hPSC CAR-NK engineering platform is a realistic strategy for off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.
BIOACTIVE MATERIALS
(2023)
Article
Immunology
Huynh Dinh Chien, Antonella Pantaleo, Kristina R. Kesely, Panae Noomuna, Karson S. Putt, Tran Anh Tuan, Philip S. Low, Francesco M. Turrini
Summary: The coadministration of imatinib with standard of care (SOC) in uncomplicated P. falciparum malaria patients led to a faster decline in parasite density and fever, without any delayed parasite clearance. The improvements were most significant in patients with the highest parasite density, where serious complications and death are most common.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Xin Liu, Boning Zhang, Yingcai Wang, Hanan S. Haymour, Fenghua Zhang, Le-cun Xu, Madduri Srinivasarao, Philip S. Low
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Sakkarapalayam M. Mahalingam, Josue D. Ordaz, Philip S. Low