Article
Biotechnology & Applied Microbiology
Andrea Perez-Iturralde, Beatriz Carte, Rafael Aldabe
Summary: The study found that mTOR inhibitors have complex effects on AAV hepatic transduction efficiency, with rapamycin enhancing AAV transduction while RapaLink-1 and MLN0128 do not. This indicates that mTOR inhibition is not a straightforward strategy for improving AAV transduction, and more research is needed to elucidate the mechanisms involved in their effects.
HUMAN GENE THERAPY
(2021)
Article
Biochemical Research Methods
Sylvain Blois, Benjamin M. Goetz, James J. Bull, Christopher S. Sullivan
Summary: The concept of nucleic acid barcodes in pathogen genomes is easy to understand, but implementing it may be challenging due to potential issues like fitness alteration, mutation accumulation, and unintended barcode generation. In this study, approximately 5000 randomized barcodes were generated in the genome of a small DNA virus, and a post-sequencing method was developed to interpret the barcode sequences. These findings may have implications for the use of randomized barcodes in other microbial systems and provide a useful approach for future studies involving nucleic acid barcoded pathogens.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Review
Neurosciences
Henry Querfurth, Han-Kyu Lee
Summary: mTOR is involved in regulating energy metabolism, neuronal growth, insulin signaling, and autophagy, playing both beneficial and pathogenic roles in neurodegenerative diseases. Balanced actions of mTOR complexes may have implications for Alzheimer's disease, Parkinson's disease, Huntington's disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis. Beyond rapamycin, rapalogs with improved tolerability and delivery modes hold promise in treating age-related conditions.
MOLECULAR NEURODEGENERATION
(2021)
Article
Medicine, General & Internal
Shin Enosawa, Huai-Che Hsu, Yusuke Yanagi, Hitomi Matsunari, Ayuko Uchikura, Hiroshi Nagashima
Summary: To develop novel medical technologies, a genetically engineered ornithine transcarbamylase-deficient (OTCD) pig strain was established and its characteristics and treatment responsiveness were reported. The OTCD pigs were obtained through mating an OTCD carrier female with a wild-type male, with the disease phenotype only appearing in males due to X-linked recessive inheritance. Treatment with nitrogen-scavenging agents based on a clinical protocol significantly extended the survival time of the OTCD pigs.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Mohamed El-Tanani, Hamdi Nsairat, Alaa A. Aljabali, Angel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Gowhar A. Naikoo, Walhan Alshaer, Murtaza M. Tambuwala
Summary: The mammalian target of rapamycin (mTOR), a signalling system, is necessary for various cell proliferation activities. It recognizes PI3KAKT stress signals as a serine-threonine kinase. The abnormal regulation of mTOR pathway has been proven to be crucial in cancer growth and advancement. This review primarily discusses the normal functions of mTOR as well as its abnormal roles in cancer development.
Article
Cell Biology
Michela Campolo, Giovanna Casili, Marika Lanza, Alessia Filippone, Marika Cordaro, Alessio Ardizzone, Sarah Adriana Scuderi, Salvatore Cuzzocrea, Emanuela Esposito, Irene Paterniti
Summary: The study demonstrates that mTOR inhibitors, especially KU0063794, have significant benefits for cognitive and motor recovery after moderate to severe traumatic brain injury, reducing lesion volumes and alleviating neuroinflammation and neuronal death.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Alaa Abou Daher, Sahar Alkhansa, William S. Azar, Rim Rafeh, Hilda E. Ghadieh, Assaad A. Eid
Summary: Understanding the mechanisms behind diabetic nephropathy (DN) is crucial for developing effective treatments. The mTOR pathway has been identified as a key player in diabetes-induced kidney injury, through its involvement in insulin resistance, oxidative stress, and autophagy regulation.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Neurosciences
Marta Garcia-Juan, Lara Ordonez-Gutierrez, Francisco Wandosell
Summary: This study found that modulation of autophagy in astrocytes can affect the generation and degradation of beta-amyloid, which is associated with neurodegenerative diseases like Alzheimer's disease. While the inhibition of MTORC1 reduced beta-amyloid secretion through moderate autophagy induction, increased activity of AMPK had different effects on beta-amyloid secretion. These findings suggest that AMPK plays a significantly different role in astrocytes compared to other cell types.
Article
Ophthalmology
Nozomi Igarashi, Megumi Honjo, Makoto Aihara
Summary: Glaucoma, the second leading cause of blindness worldwide, is often treated with trabeculectomy, but this surgery can lead to excessive scarring and tissue fibrosis. Studies have shown that mTOR inhibitors may offer a new treatment modality for reducing fibrotic response in human conjunctival fibroblasts and improving bleb scarring after filtration surgery.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Neurosciences
Supriya Sharma, Anil Kumar Rana, Aditi Sharma, Damanpreet Singh
Summary: This study found that rapamycin reduces seizures and associated cardiac damage by inhibiting mTOR activation in the zebrafish kindling model.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2022)
Article
Immunology
Preeti Vyas, Rajkumar Tulsawani, Divya Vohora
Summary: Recent findings show that neuroinflammation is closely related to seizures, and the PI3K/Akt/mTOR pathway is speculated to be a potential target for treating neuroinflammation-mediated seizures and neurodegeneration. In a study on mice, PI3K inhibitors buparlisib and dactolisib were found to be effective in prolonging seizure latency and reducing neuronal loss, while rapamycin showed some resistance. The study suggests that targeting the PI3K pathway may offer new approaches for seizure therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Ecem Sevim, Salma Siddique, Madhavi Latha S. Chalasani, Susan Chyou, William D. Shipman, Orla O'Shea, Joanna Harp, Oral Alpan, Stephane Zuily, Theresa T. Lu, Doruk Erkan
Summary: This study investigated the activation of the mammalian target of rapamycin (mTOR) in the skin of patients with livedo and antiphospholipid antibodies (aPL). The results showed increased mTOR activity in the skin of aPL-positive patients, which may have implications for further research on the mTOR pathway in these patients.
JOURNAL OF RHEUMATOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Barbara E. Staehli, Roland Klingenberg, Dik Heg, Mattia Branca, Robert Manka, Ioannis Kapos, Oliver Mueggler, Andrea Denegri, Rahel Kesterke, Florence Berger, Julia Stehli, Alessandro Candreva, Arnold von Eckardstein, David Carballo, Christian Hamm, Ulf Landmesser, Francois Mach, Tiziano Moccetti, Christian Jung, Malte Kelm, Thomas Muenzel, Giovanni Pedrazzini, Lorenz Raeber, Stephan Windecker, Christian Templin, Christian M. Matter, Thomas F. Luescher, Frank Ruschitzka
Summary: The CLEVER-ACS trial evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI, but early mTOR inhibition with everolimus did not reduce MI size or MVO at 30 days.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Article
Physiology
Bahetiyaer Huwatibieke, Wenzhen Yin, Lingchao Liu, Yuxin Jin, Xinxin Xiang, Jingyan Han, Weizhen Zhang, Yin Li
Summary: The study demonstrates that the mTOR signaling pathway affects the transformation of adipocytes by regulating mitochondrial quality control in brown adipocytes. Activation of mTOR signaling inhibits the mitochondrial quality control and promotes the transformation from brown to white adipocytes, while inhibition of mTOR signaling enhances mitochondrial quality control and inhibits the phenotypic shift.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Cecilia Flores-Clemente, Maria Ines Nicolas-Vazquez, Elvia Mera Jimenez, Maricarmen Hernandez-Rodriguez
Summary: Alzheimer's disease (AD) is the principal cause of dementia among the elderly, with changes in the histaminergic system related to cognitive impairment in AD patients. Increasing histamine levels by inhibiting histamine N-methyltransferase (HNMT) could be used as a co-therapy in AD patients.
Article
Statistics & Probability
Jingqin Luo, Feng Gao, Jingxia Liu, Guoqiao Wang, Ling Chen, Anne M. Fagan, Gregory S. Day, Jonathan Voeglein, Jasmeer P. Chhatwal, Chengjie Xiong
Summary: Bivariate correlation coefficients are commonly used in medical research to assess the relationship between two variables. In a family-type clustered design, BCCs can be defined and estimated at various hierarchical levels. Simulation studies were conducted to evaluate the performance of proposed estimators.
JOURNAL OF APPLIED STATISTICS
(2022)
Letter
Oncology
Sena Kim, Kidist Ashami, Sora Lim, Karl Staser, Kiran Vij, Srikanth Santhanam, Julie Ritchey, Sarah Peterson, Feng Gao, Matthew A. Ciorba, Matthew L. Cooper, John F. DiPersio, Jaebok Choi
Article
Oncology
Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Shilpa Sanapala, Suzanne Scheaffer, Xiaofan Guo, Sonika Dahiya, David H. Gutmann
Summary: The study identified ITGAL/CD11A as a critical microglia regulator of LGG biology, with implications for future stroma-targeted brain tumor treatment strategies.
Article
Hematology
Jingyu Xiang, Min Shi, Mark A. Fiala, Feng Gao, Michael P. Rettig, Geoffrey L. Uy, Mark A. Schroeder, Katherine N. Weilbaecher, Keith E. Stockerl-Goldstein, Shamim Mollah, John F. DiPersio
Summary: Mobilized peripheral blood has become the primary source of hematopoietic stem cells. This study compared different mobilization regimens and developed a machine learning model to predict inadequate stem cell yields in allogeneic donors.
Article
Biology
Horng-Shiuann Wu, F. Gao, L. Yan, C. Given
Summary: The study found that light therapy can significantly improve post-treatment fatigue and subjective sleep quality in female survivors of breast cancer who still experience fatigue and sleep disruption 1-3 years after completing chemotherapy and/or radiation. Additionally, unexpected benefits of dim light on sleep were observed, improving some sleep parameters.
CHRONOBIOLOGY INTERNATIONAL
(2022)
Article
Cell Biology
Corina Anastasaki, Paola Orozco, David H. Gutmann
Summary: Neurofibromatosis type 1 is a rare neurogenetic syndrome caused by mutations in the NF1 gene. The encoded protein, neurofibromin, functions as a negative regulator of RAS activity. However, neurofibromin may have additional functions beyond the canonical RAS pathway regulation.
DISEASE MODELS & MECHANISMS
(2022)
Article
Oncology
Elizabeth C. Cordell, Mahmoud S. Alghamri, Maria G. Castro, David H. Gutmann
Summary: The brain tumor microenvironment contains various nonneoplastic cells, which play important roles in the formation and progression of brain cancers. This review discusses the roles of T cells in low- and high-grade glioma formation and progression, as well as the potential uses of modified T lymphocytes for brain cancer therapeutics.
Article
Multidisciplinary Sciences
Corina Anastasaki, Juan Mo, Ji-Kang Chen, Jit Chatterjee, Yuan Pan, Suzanne M. Scheaffer, Olivia Cobb, Michelle Monje, Lu Q. Le, David H. Gutmann
Summary: Neuronal activity plays a crucial role in central and peripheral nervous system cancers. NF1 mutations modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production. In mouse models, reduced HCN channel function driven by Nf1 mutations leads to tumor growth in both central and peripheral nervous system.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Alice F. Bewley, Titilope M. Akinwe, Tychele N. Turner, David H. Gutmann
Summary: NF1 variants in sporadic tumors differ from those in NF1 individuals in terms of type, location, and pathogenicity. Many NF1 variants in sporadic cancers are not pathogenic and may be passenger variants or hypomorphic alleles. Further research is needed to define their roles in nonsyndromic cancer.
NEUROLOGY-GENETICS
(2022)
Article
Oncology
Till Milde, Jason Fangusaro, Michael J. Fisher, Cynthia Hawkins, Fausto J. Rodriguez, Uri Tabori, Olaf Witt, Yuan Zhu, David H. Gutmann
Summary: Pediatric low-grade gliomas (pLGGs) are common brain tumors in young children, which often result in chronic tumor- and therapy-related morbidities. The growth of pLGGs is influenced by genetic alterations and nonneoplastic cells in the microenvironment. Preclinical models are necessary to identify potential drugs for clinical evaluation and improve treatment for children with pLGGs.
Editorial Material
Medicine, Research & Experimental
David H. Gutmann
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Review
Oncology
Yunshuo Tang, David H. Gutmann
Summary: Optic pathway glioma (OPG) occurs in a significant number of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. While often benign and slow growing, some patients with NF1-OPGs experience symptoms such as vision loss and precocious puberty. Studies using genetically engineered Nf1-OPG mouse models have provided valuable insights into the molecular and cellular pathways of optic gliomagenesis and identified potential new treatments. Research focusing on determining the factors underlying optic glioma development and tumor-induced optic nerve injury will contribute to personalized risk assessment and improved treatment for children with NF1-OPG.
CANCER MANAGEMENT AND RESEARCH
(2023)
Article
Hematology
Michael Slade, Mark A. Fiala, Marie Kirchmeyer, Jeff King, Feng Gao, Mark A. Schroeder, A. Keith Stewart, Keith Stockerl-Goldstein, Christine Chen, Ravi Vij
Summary: This study investigates the use of elotuzumab, pomalidomide, and dexamethasone (EPd) as salvage therapy prior to and maintenance after second autologous hematopoietic cell transplantation (AHCT2) for relapsed multiple myeloma. The results show that EPd maintenance after AHCT2 is safe and tolerable, with similar 1-year progression-free survival (PFS) and median PFS compared to previous studies.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Oncology
Nicole M. Brossier, Jennifer M. Strahle, Samuel J. Cler, Michael Wallendorf, David H. Gutmann
NEURO-ONCOLOGY ADVANCES
(2022)
Article
Hematology
Lawrence Wayne Liu, Alicia Yn, Feng Gao, Marissa Olson, Mallory Crain, Ramzi Abboud, Peter Westervelt, Camille Abboud, Ravi Vij, Keith Stockerl-Goldstein, Iskra Pusic, Amanda F. Cashen, Mark A. Schroeder
Summary: Letermovir is effective in preventing CMV infection in CMV seropositive recipients. This study provides data on the incidence of csCMVi and overall survival beyond the initial 24 weeks after alloSCT. It also identifies risk factors for CMV-related mortality and suggests the possible need for extended use of letermovir.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)