The mRNA vaccine route from injection site to critical immunologic tissues, as well as the localization of protein antigen following intramuscular (i.m.) administration, is crucial to generating an effective immune response. Here, we quantified mRNA at the injection site, lymph nodes, and in select tissues. mRNA was primarily present 24 h after administration and then rapidly degraded from local and systemic tissues. Histological analyses of mRNA and expressed protein at the site of administration and in the lymph nodes following i.m. administration of our vaccine in rodents and nonhuman primates (NHPs) were completed, and mRNA and protein expression were detected in tissue resident and infiltrating immune cells at the injection site. In addition, high levels of protein expression were observed within subcapsular and medullary sinus macrophages in draining lymph nodes. More important, results were similar between rodents and NHPs, indicating cross-species similarities.
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http://dx.doi.org/10.1016/j.omtn.2023.102083 | DOI Listing |
Mol Ther
January 2025
Department of Molecular Medicine, University of Southern Denmark; Odense, 5230, Denmark. Electronic address:
Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.
View Article and Find Full Text PDFMol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFBMC Plant Biol
January 2025
School of Engineering, Dali University, Dali, Yunnan Province, China.
The homeotic transformation of stamens into pistil-like structures (pistillody) causes cytoplasmic male sterility (CMS). This phenomenon is widely present in plants, and might be induced by intracellular communication (mitochondrial retrograde signaling), but its systemic regulating mechanism is still unclear. In this study, morphological observation showed that the stamens transformed into pistil-like structures, leading to flat and dehiscent pistils, and fruit set decrease in sua-CMS (MS K326, somatic fusion between Nicotiana.
View Article and Find Full Text PDFJ Ovarian Res
January 2025
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China.
Background: Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive.
Methods: We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators.
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