Aim: To characterize changes in the cornea nerve and pain responses in fungal keratitis (FK).
Methods: A retrospective analysis of confocal microscopy images of 11 FK corneas was performed, and the results were compared with those for 11 normal corneas. Subbasal corneal nerves were analyzed for total nerve number, main nerve trunk number, branching patterns and tortuosity. C57BL/6 mice were infected with . Disease severity was determined through clinical scoring and slit lamp photography. Corneas were harvested at 1, 3, 5, and 7d post infection (p.i.) and assessed for β III tubulin. Corneal mechanical sensitivity thresholds were detected by von Frey test. β-endorphin (β-EP) and µ receptor protein expression was detected through Western blotting.
Results: Total nerve number, main nerve trunk number, and nerve branching were significantly lower in FK patients than in controls, but tortuosity was not significantly different. In infected mice, subbasal nerve density decreased from 1d p.i., reaching a minimum at 5d p.i. Clinical scores rose at 1d p.i., peaked at 3d p.i., and decreased at 5d p.i. Mechanical sensitivity thresholds showed the same trends. β-EP and µ receptor protein expression increased after infection.
Conclusion: Corneal nerve density is lower in FK patients and -infected mice than in controls. Pain sensitivity decreases with postinfection corneal ulcer aggravation. β-EP and µ receptor proteins are both upregulated in infected mouse corneas.
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http://dx.doi.org/10.18240/ijo.2020.01.01 | DOI Listing |
Neuro Oncol
January 2025
Department of Medicine, Division of Experimental Medicine, McGill University.
Background: Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma.
View Article and Find Full Text PDFJ Clin Oncol
January 2025
Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Chinese University of China, Shatin, Hong Kong Special Administrative Region, China.
Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
January 2025
The University of Texas Medical Branch at Galveston, Microbiology and Immuology, Galveston, Texas, United States.
Exposure to influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) is well-known to increase the risk of pneumonia in humans. Type I interferon (IFN-I) is a hallmark response to acute viral infections, and alveolar macrophages (AMs) constitute the first line of airway defense against opportunistic bacteria. Our study reveals that virus-induced IFN-I receptor (IFNAR1) signaling directly impairs AM-dependent antibacterial protection.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.
View Article and Find Full Text PDFSci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
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