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Introduction: Artesunate, a derivative of artemisinin, has anti-malarial effects, and in recent years has also been reported to have anti-tumor activity. However, its anti-tumor mechanisms are not well understood.Methods: In this study, we focused on the targeting of Hsp90 by artesunate to inhibit tumor cell proliferation, which we examined using immunoprecipitation, a proliferation assay, flow cytometry, western blotting, a tumor xenograft animal model, and immunohistochemistry. Furthermore, to examine the tumor-suppressive effects of artesunatein nude mice, we used artesunate-loaded PLGA-PEG nanoparticles.Results: The binding of artesunate to Hsp90 was found to reduce the expression of its client proteins AKT, ERK, p-AKT, p-ERK, and EGFR, thereby blocking the cell cycle at the G0/G1 → S stage in lymphoma cells and inducing apoptosis. In addition, the results of tumor xenograft experiments revealed that artesunate reduced the expression of AKT and ERK proteins in tumor tissues, inhibited tumor proliferation, and reduced tumor size and weight. Furthermore, nanoparticle encapsulation was demonstrated to enhance the anti-cancer activity of artesunate.Discussion: We thus established that artesunate inhibits the proliferation of lymphoma cells by targeting the Hsp90 protein, and we accordingly believe that this compound has potential for development as a novelanti-tumor drug.

Physalis pubescens L. is an annual or perennial plant in the family Solanaceae It is used in traditional medicine for treating sore throats, coughs, urinary discomfort, and astringent pain, and externally for pemphigus and eczema in northern China. The proliferation inhibitory activity and mechanisms of the ethyl acetate extract (PHY-EA) from the leaves of Physalis pubescens were investigated. High performance liquid chromatography was used to identify the chemical composition of PHY-EA; sulforhodamine B was used to detect the proliferation inhibitory effect of PHY-EA on MCF-7, CA-46, Hela, HepG2, B16, and other tumor cells; flow cytometry was used to detect the effect of PHY-EA on the lymphoma cell cycle and apoptosis; Western blot was used to detect the expression of the cycle- and apoptosis-related proteins. The expression of Ki-67 and cleaved caspase 3 was detected by immunohistochemistry. The results showed that PHY-EA contained physalin B, physalin O, and physalin L. PHY-EA blocked the cell cycle of G2/M→G0/G1 in lymphoma cells and induced apoptosis in tumor cells. Mouse transplantation tumor experiments showed that PHY-EA had a significant inhibitory effect on mouse transplantation tumors, and the tumor volume and weight were significantly reduced. In conclusion, PHY-EA has a good antiproliferative effect on Burkkit lymphoma, indicating its potential medicinal value.

To study the antitumor activity of compound 3-desoxysulforaphane (3-DSC) isolated from Caesalpinia sinensis, SRB assay, clone formation assay, flow cytometric cell cycle assay, scratch assay, transwell assay, and molecular docking were used to investigate the inhibitory effect of 3-DSC on HeLa and PC3 cells. The results showed that 3-DSC inhibited the cell migration and invasion by down-regulating expression of N-cadherin, Vimentin, MMP-2, and MMP-9 in HeLa and PC3 cells; It also inhibits cell proliferation by promoting the expression of CDK1 (cyclin-dependent kinases 1) and CDK2 (cyclin-dependent kinases 2), which arrests the tumor cell cycle at G2 phase. 3-DSC inhibits phosphorylation of AKT and ERK and upregulates the expression of the tumor suppressor gene p53. Molecular docking results confirmed that 3-DSC could bind firmly to AKT. In conclusion, 3-DSC inhibited the proliferation, migration and invasion of HeLa and PC3 cells.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low- level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. After 6 months of extremely low sporadic DUX4 expression, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capillary loss, fibrosis, and atrophy. We investigated the transcriptional profile of whole muscle as well as endothelial cells and fibroadiopogenic progenitors (FAPs). Strikingly, differential gene expression profiles of both whole muscle and, to a lesser extent, FAPs, showed significant overlap with transcriptional profiles of MRI-guided human FSHD muscle biopsies. These results demonstrate a pathophysiological similarity between disease in muscles of iDUX4pA-HSA mice and humans with FSHD, solidifying the value of chronic rare DUX4 expression in mice for modeling pathological mechanisms in FSHD and highlighting the importance FAPs in this disease., Introduction Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent (1) and slowly progressive myopathy caused by genetic mutations (2, 3), leading to the loss of epigenetic repression (4) of tandem copies [...]

Circadian regulation of gene expression is prevalent and plays critical roles in cell differentiation. However, its roles in the reprogramming of differentiated cells remain largely unknown. Here, we found that one of the master circadian regulators PER1 promoted virus-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to induced neurons (iNs) and induced pluripotent stem cells (iPSCs). Unexpectedly, PER1 achieved this by repressing inflammatory activation of contaminating macrophages in the MEF culture, rather than by directly modulating the reprogrammability of MEFs. More specifically, we found that transduced viruses activated inflammatory genes in macrophages, such as Tnf encoding TNFα, one of the central inflammatory regulators and an autocrine activator of macrophages. TNFα inhibited iN reprogramming, whereas a TNFα inhibitor promoted iN reprogramming, connecting the inflammatory responses to iN reprogramming. In addition, macrophages were induced to proliferate and mature by non-macrophage cells serving as feeders, which also supported up-regulation of TNFα in macrophages without virus transduction. Furthermore, the 2 inflammatory responses were repressed by the circadian regulator PER1 in macrophages, making reprogrammability dependent on time-of-day of virus transduction. Similar results were obtained with iPSC reprogramming, suggesting a wide occurrence of macrophage-mediated inhibition of cell reprogramming. This study uncovers mechanistic links between cell reprogramming, bystander inflammatory macrophages, and circadian rhythms, which are particularly relevant to in vivo reprogramming and organoid formation incorporating immune cells. Circadian regulation of gene expression plays critical roles in cell differentiation, but what about reprogramming of differentiated cells? This study shows that contaminating macrophages in fibroblast culture play unsuspected inhibitory roles during reprogramming to neurons and pluripotent stem cells, controlled by the circadian rhythm gene Per1. [ABSTRACT FROM AUTHOR]