Diffuse large B-cell lymphoma (DLBCL), a subtype of non-Hodgkin's lymphoma, is the most common lymphoid malignancy in the Western world. Treatment of DLBCL has been greatly improved in recent years with the addition of the monoclonal antibody Rituximab to the gold standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) chemotherapy regimen, but these treatments are often ineffective in patients with highly aggressive disease or patients of advanced age. While CAR-T cells have further advanced the treatment landscape of DLBCL, these often come at significant costs such as toxicity and financial costs for patients.
View Article and Find Full Text PDFRotenone, a naturally occurring compound derived from the roots of tropical plants, is used as a broad-spectrum insecticide, piscicide, and pesticide. It is a classical, high-affinity mitochondrial complex I inhibitor that causes not only oxidative stress, α-synuclein phosphorylation, DJ-1 (Parkinson's disease protein 7) modifications, and inhibition of the ubiquitin-proteasome system but it is also widely considered an environmental contributor to Parkinson's disease (PD). While prodromal symptoms, such as loss of smell, constipation, sleep disorder, anxiety/depression, and the loss of dopaminergic neurons in the substantia nigra of rotenone-treated animals, have been reported, alterations of metabolic hormones and hyperinsulinemia remain largely unknown and need to be investigated.
View Article and Find Full Text PDFThe neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA).
View Article and Find Full Text PDFSpinal cord injury (SCI) is a debilitating condition characterized by damage to the spinal cord resulting in loss of function, mobility, and sensation with no U.S. Food and Drug Administration-approved cure.
View Article and Find Full Text PDFSpinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy.
View Article and Find Full Text PDFSpinal cord injury (SCI) causes significant mortality and morbidity. Currently, no FDA-approved pharmacotherapy is available for treating SCI. Previously, low doses of estrogen (17β-estradiol, E2) were shown to improve the post-injury outcome in a rat SCI model.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2022
Parkinson's disease (PD) is a progressive, neurodegenerative condition of the central nervous system (CNS) affecting 6.3 million people worldwide with no curative treatments. Current therapies aim to mitigate PD's effects and offer symptomatic relief for patients.
View Article and Find Full Text PDFSpinal Cord Injury (SCI) is a debilitating condition characterized by damage to the spinal cord, resulting in loss of function, mobility, and sensation. Although increasingly prevalent in the US, no FDA-approved therapy exists due to the unfortunate complexity of the condition, and the difficulties of SCI may be furthered by the development of SCI-related complications, such as osteoporosis. SCI demonstrates two crucial stages for consideration: the primary stage and the secondary stage.
View Article and Find Full Text PDFSpinal cord injury (SCI) is associated with devastating neurological deficits affecting more than 11,000 Americans each year. Although several therapeutic agents have been proposed and tested, no FDA-approved pharmacotherapy is available for SCI treatment. We have recently demonstrated that estrogen (E2) acts as an antioxidant and anti-inflammatory agent, attenuating gliosis in SCI.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
December 2020
Although relatively few in number compared to astrocytes and neurons, microglia demonstrate multiple, varied neuroimmunological functions in the central nervous system during normal and pathological states. After injury to the brain or spinal cord, microglia express beneficial pro- and anti-inflammatory phenotypes at various stages of recovery. However, prolonged microglial activation following injury has been linked to impaired parenchymal healing and functional restoration.
View Article and Find Full Text PDFExtra-nigral central nervous system sites have been found to be affected in Parkinson's disease (PD). In addition to substantia nigra, degeneration of spinal cord motor neurons may play a role in the motor symptoms of PD. To this end, hybrid rodent VSC 4.
View Article and Find Full Text PDFSpinal cord injury (SCI) patients sustain significant functional impairments; this is causally related to restricted neuronal regeneration after injury. The ensuing reactive gliosis, inflammatory cascade, and glial scar formation impede axonal regrowth. Although systemic anti-inflammatory agents (steroids) have been previously administered to counteract this, no current therapeutic is approved for post-injury neuronal regeneration, in part because of related side effects.
View Article and Find Full Text PDFEnolase inhibition is a potential therapeutic strategy currently being investigated for treatment of spinal cord injury (SCI) as it reduces pro-inflammatory cytokines and chemokines, alters metabolic factors, and reduces gliosis in acute SCI. Herein, the role of enolase in SCI has been examined to better understand the effects of this enzyme on inflammation, metabolic hormones, glial cell activation, and neuroprotection under these shorter injury conditions. Immunohistochemical analyses of inflammatory markers vimentin, Cox-2, and caspase-1 indicated that enolase inhibition attenuated the elevated levels of inflammation seen following SCI.
View Article and Find Full Text PDFParkinson's disease (PD), a debilitating progressive degenerative movement disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra (SN), afflicts approximately one million people in the U.S., including a significant number of Veterans.
View Article and Find Full Text PDFThis study examines the cytokine/chemokine profile of a 62-year-old African American male with progressive multiple sclerosis (MS). MRI images of the MS patient demonstrated generalized white matter involvement with multiple lesions in the periventricular area. A 42-plex Discovery Assay® (Eve Technologies) of the patient's plasma and peripheral blood mononuclear cells (PBMCs) supernatant or PBMC-derived T cell supernatant samples from two separate clinic visits revealed vastly differing cytokine/chemokine levels.
View Article and Find Full Text PDFProg Mol Biol Transl Sci
May 2020
Parkinson's disease (PD) devastates 6.3 million people, ranking it as one of the most prevalent neurodegenerative motor disorders worldwide. PD patients may manifest symptoms of postural instability, bradykinesia, and resting tremors as a result of increasing α-synuclein aggregation and neuron death with disease progression.
View Article and Find Full Text PDFThe cytokine/chemokine expression signature of a 60-year-old African American male with relapsing-remitting multiple sclerosis (RRMS) was analyzed using patient blood samples obtained from two separate visits to the clinic. Thirty-six different cytokines, chemokines, and growth factors were detected in the plasma of the RRMS patient using a multiplexed bead-based immunoassay. Results indicated that at least ten of these factors with a concentration of > 100 pg/mL are identified as pro-inflammatory.
View Article and Find Full Text PDFNeurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells.
View Article and Find Full Text PDFMyelin basic protein (MBP) is a major target of T cells in lesions of multiple sclerosis (MS) patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Interactions between the major histocompatibility complex II containing antigenic peptides and the T cell receptor activate CD4+ T cells that perpetuate EAE and MS. Previously reported data has shown that treating with an altered peptide ligand (APL) in which the normal antigenic peptide sequence of MBP has been slightly changed at T cell contact positions is helpful in reducing disease in both rodents and humans.
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