We recently reported that a DNA plasmid coding p62-SQSTM1 acts as an effective anti tumor vaccine against both transplantable mouse tumors and canine spontaneous mammary neoplasms. Here we report the unexpected finding that intramuscular delivery of p62 DNA exerts a powerful anti-osteoporotic activity in a mouse model of inflammatory bone loss (i.e, ovariectomy) by combining bone-sparing and osteo-synthetic effects. Notably, the suppression of osteoporosis by p62DNA was associated with a sharp down-regulation of master inflammatory cytokines, and up-regulation of endogenous p62 protein by bone-marrow stromal cells. The present data provide a solid rational to apply p62 DNA vaccine as a safe, new therapeutic for treatment of inflammatory related bone loss diseases.
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http://dx.doi.org/10.18632/oncotarget.2884 | DOI Listing |
Sci Rep
January 2025
School of Forensic Medicine, Guizhou Medical University, Guiyang, 550004, China.
DNA methylation modifications are an important mechanism affecting the process of atherosclerosis (AS). Previous studies have shown that Galectin-8 (GAL8) DNA methylation level is associated with sudden death of coronary heart disease or acute events of coronary heart disease. However, the mechanism of GAL8 DNA methylation and gene expression in AS has not been elucidated, prompting us to carry out further research on it.
View Article and Find Full Text PDFAutophagy
January 2025
Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Brain Science Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, 855 N. Wolfe St., Rangos 275, Baltimore, MD, 21205, USA.
The GC hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFThe GC hexanucleotide repeat expansion in the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFCell Death Dis
December 2024
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital and School of Basic Medical Science, Central South University, Changsha, Hunan, China.
Drug resistance and recurrence are still the bottlenecks in the clinical treatment of ovarian cancer (OC), seriously affecting patients' prognosis. Therefore, it is an urgent challenge for OC to be overcome towards precision therapy by studying the mechanism of OC drug resistance, finding new drug resistance targets and developing new effective treatment strategies. In this study, we found that lncRNA LOC730101 played an essential role in attenuating drug resistance in OC.
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