Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.
Though small-molecule drugs play a crucial role in cancer treatment, intrinsic issues such as poor solubility and systematic toxicity have considerably mitigated their anticancer functions and caused unwanted side effects. To achieve satisfying therapeutic efficiency, it is essential to develop innovative targeting systems for precise and efficient delivery of anticancer drugs. In this work, a hierarchical selfassembly strategy was applied to fabricate a core−shell nanoarchitecture composed of a DNA octahedral wireframe and chemodrug-functionalized Sgc8c aptamer. The integrated enhanced permeability and retention effect of the DNA nanostructure and active targeting ability of the Sgc8c aptamer allowed the highly selective chemodrug delivery and in vivo efficient imaging and treatment. The advantage of our multifunctional nanostructure was further highlighted by its impressive serum stability, excellent accumulation ability, deep penetration capability, significantly improved therapeutic efficacy, and favorable biosafety. This study showed promising potential of such a core−shell DNA nanoarchitecture in precise drug loading control, drug delivery, and personal medicine.
Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.
Amphiphilic DNA block copolymers have been utilized in preparing self-assembled amphiphilic structures in aqueous solution. These block copolymers usually contain specifically designed hydrophobic regions, and typically assemble under near-physiological conditions. Here, we report self-assembly of spherical micelles and one-dimensional nanorods under acidic conditions from cholesterol-conjugated DNA strands (Cholesterol-DNA). Further study also revealed that the nanorods were hierarchically assembled from the micelle nanostructures. The morphology of the nanorod assemblies can be tuned by altering solution condition and the design of Cholesterol-DNA. The self-assembly of Cholesterol-DNA nanostructures under acidic conditions and the discovery of the relationship between the nanorods and the micelles can provide new insights for future design of self-assemblies of amphiphilic DNA block copolymers.
The endocrine-related cancers and hormones are undoubtedly highly interconnected. How hormones support or repress tumor induction and progression has been extensively profiled. Furthermore, advances in understanding the role of glutamine metabolism in mediating tumorigenesis and development, coupled with these in-depth studies on hormone (e.g., estrogen, progesterone, androgen, prostaglandin, thyroid hormone, and insulin) regulation of glutamine metabolism, have led us to think about the relationship between these three factors, which remains to be elucidated. Accordingly, in this review, we present an updated overview of glutamine metabolism traits and its influence on endocrine oncology, as well as its upstream hormonal regulation. More importantly, this hormone/glutamine metabolism axis may help in the discovery of novel therapeutic strategies for endocrine-related cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.