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Advancements in Transdermal Drug Delivery Systems: Harnessing the Potential of Macromolecular Assisted Permeation Enhancement and Novel Techniques.
AAPS PharmSciTech
January 2025
Department of Pharmaceutics, School of Pharmaceutical Science, Siksha 'O' Anusandhan University, Bhubaneswar, 751003, Odisha, India.
Transdermal drug delivery (TDD) represents a transformative paradigm in drug administration, offering advantages such as controlled drug release, enhanced patient adherence, and circumvention of hepatic first-pass metabolism. Despite these benefits, the inherent barrier function of the skin, primarily attributed to the stratum corneum, remains a significant impediment to the efficient permeation of therapeutic agents. Recent advancements have focused on macromolecular-assisted permeation enhancers, including carbohydrates, lipids, amino acids, nucleic acids, and cell-penetrating peptides, which modulate skin permeability by transiently altering its structural integrity.
View Article and Find Full Text PDFConditional Deletion of Gremlin-1 in Cathepsin K-expressing Mature Osteoclasts Altered the Skeletal Response to Calcium Depletion in Sex-Dependent Manner.
Calcif Tissue Int
January 2025
Musculoskeletal Disease Center (151), Jerry L. Pettis Memorial VA Medical Center, VA Loma Linda Healthcare System, 11201 Benton Street, Loma Linda, CA, 92357, USA.
This study assessed the novel concept that osteoclast-derived Grem1 has regulatory functions in the skeletal response to calcium stress using an osteoclastic Grem1 conditional knockout (cKO) mouse model. The calcium stress was initiated by feeding cKO mutants and wildtype (WT) littermates a calcium-deficient diet for 2 weeks. Deletion of Grem1 in mature osteoclasts did not affect developmental bone growth nor basal bone turnover.
View Article and Find Full Text PDFRepeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice.
Sci Rep
January 2025
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change.
View Article and Find Full Text PDFCarbonic anhydrase 2-derived drug-responsive domain regulates membrane-bound cytokine expression and function in engineered T cells.
Commun Biol
January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
View Article and Find Full Text PDFAn antagonistic role of clock genes and lima1 in kidney regeneration.
Commun Biol
January 2025
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, 430072, Wuhan, China.
The circadian clock genes are known important for kidney development, maturation and physiological functions. However, whether and how they play a role in renal regeneration remain elusive. Here, by using the single cell RNA-sequencing (scRNA-seq) technology, we investigated the dynamic gene expression profiles and cell states after acute kidney injury (AKI) by gentamicin treatment in zebrafish.
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