Apolipoprotein D is crucial for promoting perineural invasion in salivary adenoid cystic carcinoma
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Emerging roles of extracellular vesicles in oral and maxillofacial areas
The oral and maxillofacial region is a highly complex area composed of multiple tissue types and bears various critical functions of the human body. Diseases in this region pose significant diagnostic and management challenges; therefore, exploring new strategies for early diagnosis, targeted treatment, and tissue reconstruction is key to improving patient prognosis and quality of life. Extracellular vesicles are a group of heterogeneous lipid-bilayer membrane structures secreted by most cell types, including exosomes, microvesicles, and apoptotic bodies. Present in various body fluids and tissues, they act as messengers via the transfer of nucleic acids, proteins, and metabolites to recipient cells. To date, studies have revealed the different roles of extracellular vesicles in physiological or pathological processes, as well as applications in disease diagnosis, prognosis, and treatment. The importance and tissue specificity of the dental and maxillofacial tissues indicate that extracellular vesicles derived from this region are promising for further research. This paper reviews the published data on extracellular vesicles derived from cells, body fluids, and tissues in oral and maxillofacial regions, summarizes the latest advances in extracellular vesicles from extensive sources, and concludes with a focus on the current research progress and application prospects of engineered exosomes in oral science.
Organoids in the oral and maxillofacial region: present and future
The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.
Live imaging of the extracellular matrix with a glycan-binding fluorophore
All multicellular systems produce and dynamically regulate extracellular matrices (ECMs) that play essential roles in both biochemical and mechanical signaling. Though the spatial arrangement of these extracellular assemblies is critical to their biological functions, visualization of ECM structure is challenging, in part because the biomolecules that compose the ECM are difficult to fluorescently label individually and collectively. Here, we present a cell-impermeable small-molecule fluorophore, termed Rhobo6, that turns on and red shifts upon reversible binding to glycans. Given that most ECM components are densely glycosylated, the dye enables wash-free visualization of ECM, in systems ranging from in vitro substrates to in vivo mouse mammary tumors. Relative to existing techniques, Rhobo6 provides a broad substrate profile, superior tissue penetration, non-perturbative labeling, and negligible photobleaching. This work establishes a straightforward method for imaging the distribution of ECM in live tissues and organisms, lowering barriers for investigation of extracellular biology.
The evolution and maintenance of trioecy with cytoplasmic male sterility
Trioecy, the co-existence of females, males and hermaphrodites, is a rare sexual system in plants that may be an intermediate state in transitions between hermaphroditism and dioecy. Previous models have identified pollen limitation as a necessary condition for the evolution of trioecy from hermaphroditism. In these models, the seed-production and pollen production of females and males relative to those of hermaphrodites, respectively, are compromised by self-fertilization by hermaphrodites under pollen- limitation. Here, we investigate the evolution of trioecy via the invasion of cytoplasmic male sterility (CMS) into androdioecious populations in which hermaphrodites co-occur with males and where the male determiner is linked to a (partial) fertility restorer. We show that the presence of males in a population renders invasion by CMS more difficult. However, the presence of males also facilitates the maintenance of trioecy even in the absence of pollen limitation by negative frequency-dependent selection, because males reduce the transmission of CMS by females by siring sons (which cannot transmit CMS). We discuss our results in light of empirical observations of trioecy in plants and its potential role in the evolution of dioecy.
Insufficient expression of COL6A1 promotes the development of early-onset severe preeclampsia by inhibiting the APJ/AKT signaling pathway
Early-onset severe preeclampsia (eosPE) is one of the most severe complications of pregnancy. To identify the genes related to the development of eosPE. We downloaded and integrated analyzed microarray data from GSE44711, GSE66273, and GSE74341, which contains the expression profile of placental tissues from patients with eosPE and healthy controls. Our analysis revealed that collagen type VI alpha 1 (COL6A1) was downregulated in the eosPE placenta compared to normal pregnancy. COL6A1 promoted the migration, invasion and tube formation ability of HTR8/SVneo cells, HUVECs and primary extravillous trophoblasts (EVTs). To explore the underlying mechanisms, we conducted transcriptome sequencing, which indicated that the Apelin/APJ signaling pathway was affected by COL6A1 knockdown. In addition, we found that APJ expression was lower in the placental tissue of patients with eosPE compared to healthy pregnancies. Inhibition of APJ suppressed the invasion, migration, and tube formation abilities of trophoblasts. We also observed that COL6A1 increased the levels of p-AKT and p-mTOR, while the APJ inhibitor ML221 impaired this effect. Furthermore, transwell and tube formation assays demonstrated that ML221 attenuated the capabilities enhanced by COL6A1, an effect that could be rescued by the AKT activator SC79. Overall, these findings indicate that insufficient expression of COL6A1 attenuates the migration, invasion, and endothelial-like tube formation of HTR8/SVneo cells and primary EVTs via the APJ/AKT/mTOR pathway, thereby promoting the development of eosPE.
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