Review
Biochemistry & Molecular Biology
Carla Rodriguez-Mogeda, Sabela Rodriguez-Lorenzo, Jiji Attia, Jack van Horssen, Maarten E. Witte, Helga E. de Vries
Summary: Multiple sclerosis is an inflammatory disease where B cells play a crucial role in the pathogenesis, migrating into the central nervous system through various routes. Understanding the routes of B cell entry into the inflamed CNS is essential for comprehending the disease.
Article
Clinical Neurology
Sebok K. Halder, Richard Milner
Summary: Fifty years of research on multiple sclerosis have provided significant insights into this neurological disease, revealing its characteristics and raising questions about the initial trigger of the inflammatory demyelinating process. Recent studies suggest that hypoxia, in addition to the immune system, may play a role in disease progression, leading researchers to investigate the impact of manipulating inspired oxygen levels.
Article
Clinical Neurology
Sebok K. Halder, Richard Milner
Summary: Multiple sclerosis is an autoimmune disease that may be affected by hypoxia as a new potential trigger for the inflammatory demyelinating process. Studies have shown the presence of hypoxia in early demyelinating lesions, prompting researchers to investigate how oxygen levels impact disease progression.
Article
Pharmacology & Pharmacy
Ningbo Cai, Bingtian Xu, Xing Li, Yunyun Qin, Mengfan Li, Kechun Chen, Jiangping Xu, Haitao Wang
Summary: PDE4 inhibitor Roflumilast protects against neuronal damage caused by immune ischemia and activates Notch1/Hes1 signaling, leading to increased expression of TJ and AJ proteins and maintenance of blood-brain barrier integrity. Roflu also improves neurobehavioral outcomes and ameliorates BBB disruption in rats.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Thomas Gabriel Schreiner, Constantin Romanescu, Bogdan Ovidiu Popescu
Summary: This article reviews the role of the blood-brain barrier (BBB) in multiple sclerosis (MS) pathology, emphasizing the importance of neurovascular unit damage in MS onset and progression, as well as the impact of BBB cell alterations and immune cell penetration into the central nervous system on MS pathology.
Article
Neurosciences
Fang-fang Zhang, Hao Wang, Yan-meng Zhou, Hai-yang Yu, Melanie Zhang, Xian Du, Dong Wang, Feng Zhang, Ying Xu, Ji-guo Zhang, Han-Ting Zhang
Summary: PDE4 inhibitors exert antinociceptive effects by regulating the cAMP-Cx43 signaling pathway in the spinal cord, increasing the expression of Cx43, and reducing mechanical hypersensitivity-induced pain.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Rodica Balasa, Laura Barcutean, Oana Mosora, Doina Manu
Summary: This review discusses the disruption of the blood-brain barrier (BBB) in multiple sclerosis (MS) pathogenesis, focusing on the impairment of the neurovascular unit (NVU) and metabolic and mitochondrial dysfunctions of BBB’s endothelial cells. It highlights the hypoxic hypothesis in MS, potential mechanisms of neurodegeneration in progressive forms of MS, and the possibility of BBB as a therapeutic target for delivering neuroprotective molecules into the central nervous system. Additionally, it explores the beneficial effects of disease-modifying therapies (DMTs) that can cross the BBB and act directly in the CNS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xinli Niu, Hongzhen Sang, Junpeng Wang
Summary: The study demonstrated that naringenin could attenuate experimental autoimmune encephalomyelitis (EAE) by maintaining the blood-brain barrier, reducing immune cell infiltration, and inhibiting the infiltration of pathogenic T cells into the central nervous system.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
S. M. Lunin, E. G. Novoselova, O. V. Glushkova, S. B. Parfenyuk, A. A. Kuzekova, T. V. Novoselova, M. G. Sharapov, E. K. Mubarakshina, R. G. Goncharov, M. O. Khrenov
Summary: This study showed that the immunomodulator thymulin and the antioxidant enzyme Prdx6 can improve the condition of blood-brain barrier (BBB) and alleviate symptoms of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Thymulin decreased immune cell activation, while Prdx6 reduced NOX1 and NOX4 gene expression in brain tissue, contributing to the improvements in BBB condition and health status. Simultaneous administration of thymulin and Prdx6 resulted in complete symptomatic restoration of mice with EAE.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Environmental Sciences
Divjot Virk, Amit Kumar, Amteshwar Singh Jaggi, Nirmal Singh
Summary: Arsenic exposure can lead to serious health problems, but the PDE-4 inhibitor rolipram shows potential in treating vascular endothelial dysfunction and dementia induced by SA in rats. This treatment improved memory, reduced oxidative stress, and inflammation in the brain.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Immunology
Walyson Coelho Costa, Vinicius Amorim Beltrami, Gabriel Henrique Campolina-Silva, Celso Martins Queiroz-Junior, Rodrigo M. Florentino, Jessica Rayssa Machado, Debora Gonzaga Martins, William Antonio Goncalves, Livia Correa Barroso, Katia Michelle Freitas, Fernando Pedro de Souza-Neto, Franciel Batista Felix, Rafaela Fernandes da Silva, Cleida Aparecida Oliveira, Niels Olsen Saraiva Camara, Milene Alvarenga Rachid, Mauro Martins Teixeira, Barbara Maximino Rezende, Vanessa Pinho
Summary: The effects of PDE-4 inhibitors rolipram and roflumilast on a doxorubicin-induced nephrotic syndrome model were evaluated. The results showed that early-stage rolipram treatment preserved glomerular filtration barrier function and reduced inflammation and renal fibrosis. Late-stage treatment with either rolipram or roflumilast also protected glomerular filtration barrier function and reduced renal tissue fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Neurosciences
Julie J. Ahn, Yusra Islam, Cheryl Clarkson-Paredes, Molly T. Karl, Robert H. Miller
Summary: Multiple sclerosis is a disease characterized by compromised blood-brain barrier and peripheral lymphocytes entering the central nervous system. Although T cells have been considered the main contributors to neuroinflammation, the success of B cell depletion therapies suggests an important role for B cells. In an animal model of MS, B cell depletion affects glial cell function and CNS vasculature.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Yuying Cen, Yuheng Shan, Jiahua Zhao, Xiaojiao Xu, Zhiyong Nie, Jiatang Zhang
Summary: This study aimed to investigate the impact of major transporters at the blood-brain barrier and blood-cerebrospinal fluid barrier on the pharmacokinetics of levofloxacin in rats. The results showed that the efflux of levofloxacin from the central nervous system involves multi-drug resistance-associated proteins, breast cancer resistance protein, and organic anion transporters. The concentrations of levofloxacin in cerebrospinal fluid can be used as a surrogate to predict the concentrations inside the brain parenchyma.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Medicine, General & Internal
Kristy Nguyen, Pierre Juillard, Simon Hawke, Georges E. Grau, Felix Marsh-Wakefield
Summary: The breakdown of the blood-brain barrier and the migration of lymphocytes play important roles in the development of multiple sclerosis. Treatment with alemtuzumab can inhibit inflammation in the central nervous system, but its effect on T cell migration needs more study.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Physiology
Omid Razi, Bakhtyar Tartibian, Ismail Laher, Karuppasamy Govindasamy, Nastaran Zamani, Silvia Rocha-Rodrigues, Katsuhiko Suzuki, Hassane Zouhal
Summary: Multiple sclerosis (MS) and COVID-19 infection are related, both causing neuroinflammation and plaque formation. Conditions related to MS that make patients more susceptible to viral infection include inflammatory status, blood-brain barrier permeability, function of CNS cells, and plaque formation. Both MS and COVID-19 infection are also associated with psychoneurological and mood disorders. Moderate exercise training can improve the health of patients with MS.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nagiua Cuomo-Haymour, Giorgio Bergamini, Giancarlo Russo, Luka Kulic, Irene Knuesel, Roland Martin, Andre Huss, Hayrettin Tumani, Markus Otto, Christopher R. Pryce
Summary: This study investigated the serum extracellular vesicle (EV) microRNAs (miRNAs) in different stages of multiple sclerosis (MS) patients and matched controls, aiming to identify MS stage-specific differential expressed miRNAs and their potential as biomarkers and relevance to the disease. The study found a moderate number of dysregulated serum EV miRNAs in CIS-remission and RRMS-relapse patients, with some miRNAs having potential as biomarkers for patient-control and CIS-RRMS differentiation. In silico analysis identified biological processes related to MS pathophysiology as the mRNA targets of RRMS-relapse-specific EV miRNAs. The findings demonstrate the potential of specific serum EV miRNAs as MS stage-specific biomarkers and provide insights into potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Mina Ghanimi Fard, Zahra Khabir, Philipp Reineck, Nicole M. Cordina, Hiroshi Abe, Takeshi Ohshima, Sagar Dalal, Brant C. Gibson, Nicolle H. Packer, Lindsay M. Parker
Summary: This study developed a novel method to target glycan receptors in different brain cell types using lectin-conjugated nanodiamonds. The results demonstrate that the uptake of lectin-conjugated nanodiamonds varies across different types of brain cells.
NANOSCALE ADVANCES
(2022)
Article
Chemistry, Analytical
Yueying Cao, Jiehua Wu, Xianlin Zheng, Yanling Lu, James A. Piper, Yiqing Lu, Nicolle H. Packer
Summary: A systematic approach was introduced to quantitatively evaluate the biological activity of antibody-conjugated UCNPs. An optimal antibody conjugation efficiency of approximately 70% was determined under specific conditions, providing a practical guideline for future studies on functionalized UCNPs.
ANALYTICA CHIMICA ACTA
(2022)
Article
Biochemistry & Molecular Biology
Josefine Ruder, Gianna Dinner, Aleksandra Maceski, Ernesto Berenjeno-Correa, Antonia Maria Mueller, Ilijas Jelcic, Jens Kuhle, Roland Martin
Summary: Autologous hematopoietic stem cell transplantation (aHSCT) is an effective treatment for multiple sclerosis (MS), which normalizes pathological processes and enhances beneficial processes. Biomarker analysis of MS patients undergoing aHSCT showed that serum levels of CXCL10, NfL, and GFAP significantly increased one month after transplantation, but returned to normal after one to two years. Levels of GFAP in cerebrospinal fluid (CSF) increased 24 months after aHSCT, indicating sustained astroglia activation. Other CSF markers remained relatively stable.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Gilbert S. Omenn, Lydie Lane, Christopher M. Overall, Charles Pineau, Nicolle H. Packer, Ileana M. Cristea, Cecilia Lindskog, Susan T. Weintraub, Sandra Orchard, Michael H. A. Roehrl, Edouard Nice, Siqi Liu, Nuno Bandeira, Yu-Ju Chen, Tiannan Guo, Ruedi Aebersold, Robert L. Moritz, Eric W. Deutsch
Summary: According to the 2022 metrics of the HUPO Human Proteome Project (HPP), protein expression has been detected for 93.2% of the predicted proteins in the human genome. The number of missing proteins has been reduced, indicating experimental progress and reclassification. Proteomics continues to yield significant findings in biological and clinical studies and integrates with other omics platforms.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Medicine, Research & Experimental
Wei Zhang, Yan Yang, Liewen Lin, Jingquan He, Jingjing Dong, Bin Yan, Wanxia Cai, Yumei Chen, Lianghong Yin, Donge Tang, Fanna Liu, Yong Dai
Summary: This study characterized the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting patient survival. The findings shed light on the functions and pathways associated with ubiquitination in CRC, as well as the potential role of FOCAD mutations in RNA localization and translation. These findings offer new opportunities for clinical treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Nima Sayyadi, Irene Justiniano, Yan Wang, Xianlin Zheng, Wei Zhang, Lianmei Jiang, Dmitry M. Polikarpov, Robert D. Willows, David Gillatt, Douglas Campbell, Bradley J. Walsh, Jingli Yuan, Yiqing Lu, Nicolle H. Packer, Yuling Wang, James A. Piper
Summary: Two molecular cytology approaches, TGiA and RiA, have been developed to detect prostate cancer cells. TGiA-OSAM showed single-cell PCa detection sensitivity, while RiA had a lower limit of detection. Both assays detected low abundance PCa cells in patient urine and showed correlation with clinical data.
SCIENTIFIC REPORTS
(2022)
Review
Biotechnology & Applied Microbiology
Wei Zhang, Douglas H. Campbell, Bradley J. Walsh, Nicolle H. Packer, Dingbin Liu, Yuling Wang
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal cancer with limited diagnostic and therapeutic options. Cancer-derived small extracellular vesicles (sEVs) show potential as non-invasive biomarkers for PDAC diagnosis and therapeutic tools.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Edward S. X. Moh, Andreas Zankl, Nicolle H. Packer
Summary: Skeletal dysplasias are rare genetic disorders that affect skeletal growth and development, causing physical deformities and other medical problems. High-throughput genome sequencing technologies have made it easier to identify the genotype of the disorder, but phenotypic outcomes may not always be represented. In this pilot study, we demonstrate the ability to phenotype patients with CHST3-related skeletal dysplasia by profiling glycosaminoglycans and sequentially identifying their potential protein carriers using freezer-induced patient urine sediments.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ha Na Kim, Zehra Elgundi, Xiaoting Lin, Lu Fu, Fengying Tang, Edward S. X. Moh, MoonSun Jung, Keerthana Chandrasekar, Florence Bartlett-Tomasetig, Candice Foster, Nicolle H. Packer, John M. Whitelock, Jelena Rnjak-Kovacina, Megan S. Lord
Summary: Growth factors play a crucial role in angiogenesis for tissue repair and regeneration. However, the clinical success of growth factor delivery has been limited. This study demonstrates that engineered short forms of perlecan can bind and activate angiogenic growth factors. Delivery of these engineered perlecan forms in chitosan scaffolds promotes angiogenesis, making them potential next generation angiogenic therapies.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Multidisciplinary Sciences
Qiaochu Liang, Caixia Ma, Shauna M. Crowley, Joannie M. Allaire, Xiao Han, Raymond W. W. Chong, Nicolle H. Packer, Hong Bing Yu, Bruce A. Vallance
Summary: Enteric bacterial pathogens, such as Citrobacter rodentium, are able to adapt to the host's intestinal environment through metabolizing sialic acid derived from mucins and utilizing it as a carbon source for growth. The bacteria also sense and display chemotactic activity toward sialic acid. Sialic acid induces the secretion of autotransporter proteins, Pic and EspC, which enhance the bacteria's ability to degrade intestinal mucus and adhere to epithelial cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Benjamin J. Pullen, Achini K. Vidanapathirana, Lauren Sandeman, Arun Everest-Dass, Daniel Kolarich, Joanne T. Tan, Peter Psaltis, Stephen Nicholls, Nicolle H. Packer, Christina A. Bursill
Article
Chemistry, Analytical
Wei Zhang, Ling Wang, Dan Li, Douglas H. Campbell, Bradley J. Walsh, Nicolle H. Packer, Qing Dong, Erkang Wang, Yuling Wang
Summary: Circulating sEVs derived from PDAC cells have potential applications in cancer diagnosis. The phenotype of sEVs is closely associated with the presence and progression of PDAC, and can be validated through various imaging techniques. The proposed SERS assay enables simultaneous detection of multiple surface membrane proteins on sEVs, providing a potential method for PDAC diagnosis and early cancer stage prediction.
ANALYTICAL METHODS
(2022)
Article
Biochemistry & Molecular Biology
Zeynep Sumer-Bayraktar, Christopher M. Fife, Frances L. Byrne, Maria Kavallaris, Nicolle H. Packer
Summary: This study provides a comprehensive protein glycome profiling of neuroblastoma cells with varying invasiveness and migratory potential, and reveals distinct membrane glycan features of cells grown under 2D vs 3D culture conditions.
Article
Biochemistry & Molecular Biology
Edward S. X. Moh, Krishnatej Nishtala, Sameera Iqbal, Vasiliki Staikopoulos, Dilip Kapur, Mark R. Hutchinson, Nicolle H. Packer
Summary: The use of opioids for persistent pain treatment has increased, but it has not improved pain management outcomes. This study investigated the molecular mechanisms of opioids by analyzing proteomics and multiglycomics of cerebral spinal fluid samples from patients receiving long-term intrathecal morphine or baclofen. The study found significant differences in polysialic acid, heparan sulfate glycosaminoglycan, and O-glycan profiles between the two treatment groups, revealing previously undescribed molecular effects of opioid administration and pain management.