We hypothesized that neuropeptides released from the peripheral terminals of primary afferents play an important role in mechanical hyperalgesia after peripheral nerve injury. Nerve injury was performed on rats with lumbar 5 spinal nerve lesion (L5 SNL), which was preceded by L5 dorsal rhizotomy (L5 DR) to avoid the potential central effects induced by L5 SNL through the L5 dorsal root. L5 DR produced a short-lasting (<6 days) decrease in paw withdrawal threshold (PWT) while the following L5 SNL produced a persistent (>42 days) PWT decrease. When intraplantar injection to the affected hind paw was given immediately before L5 SNL, antagonists for both neurokinin 1 (NK1) and calcitonin gene-related peptide 1 (CGRP1) receptors delayed the onset of the PWT decrease for 2-4 days. However, when the same injection was given after L5 SNL, CGRP1, but not NK1, receptor antagonist reversed the decreased PWT for 105 min. It is suggested that peripherally released neuropeptides contribute to the generation of neuropathic pain, with substance P and CGRP contributing to its induction phase, but only CGRP to its maintenance phase.
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http://dx.doi.org/10.1016/j.neulet.2004.02.043 | DOI Listing |
Vet Sci
December 2024
Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu 18618-681, Brazil.
Canine oral melanoma (COM) is a promising target for immunomodulatory therapies aimed at enhancing the immune system's antitumor response. Given that adipose-derived mesenchymal stem cells (Ad-MSCs) possess immunomodulatory properties through cytokine release, we hypothesized that co-culturing Ad-MSCs and canine peripheral blood mononuclear cells (PBMCs) could stimulate interleukin (IL) production against melanoma cell lines (MCCLs) and help identify therapeutic targets. This study evaluated IL-2, IL-8, and IL-12 expressions in co-culture with MCCL, Ad-MSCs, and PBMCs and assessed the relationship between gene expression, cell viability, and migration.
View Article and Find Full Text PDFToxins (Basel)
December 2024
Division of Toxicology, Institute for Medical Research and Occupational Health, HR-10 000 Zagreb, Croatia.
The increasing use of products for medicinal, dietary, and recreational purposes has raised concerns about mycotoxin contamination in cannabis and hemp. Mycotoxins persist in these products' post-processing, posing health risks via multiple exposure routes. This study investigated cytotoxic and genotoxic interactions between cannabidiol (CBD) and the mycotoxin citrinin (CIT) using human cell models: SH-SY5Y, HepG2, HEK293, and peripheral blood lymphocytes.
View Article and Find Full Text PDFMol Cell Endocrinol
December 2024
Conjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, Qld 4029; School of Medicine, University of Queensland, Herston, Qld 4029; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Qld 4000, Australia. Electronic address:
Transthyretin is a thyroid hormone binding protein with a major role in the distribution of thyroid hormones to peripheral tissues. In preeclampsia, the failing placenta releases soluble endoglin into the maternal circulation causing systemic vascular dysfunction. Our group has previously shown that transthyretin binds to soluble endoglin and is taken up as a complex into hepatocytes.
View Article and Find Full Text PDFPharmacol Res
December 2024
Translational Neurodegeneration Research and Neuropathology Lab, Department of Clinical Medicine (KlinMed), Medical Faculty, University of Oslo (UiO) and Section of Neuropathology Research, Department of Pathology, Clinics for Laboratory Medicine (KLM), Oslo University Hospital (OUS), Sognsvannsveien 20, N-0372 Oslo, Norway; Institute of Nutritional Medicine (INUM) and Lübeck Institute of Dermatology (LIED), University of Lübeck (UzL) and University Medical Center Schleswig-Holstein (UKSH), Ratzeburger Allee 160, D-23538 Lübeck, Germany; Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas iela 3, LV-1004 Rīga, Latvia; School of Neurobiology, Biochemistry and Biophysics, The Georg S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, IL-6997801, Israel. Electronic address:
Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions.
View Article and Find Full Text PDFJ Control Release
December 2024
Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China; The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213003, China. Electronic address:
Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.
Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.
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