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Abstract. MicroRNAs (miRNAs) are emerging as a class of small regulatory RNAs whose alterations are implicated in the initiation and progression of human cancers. Our study showed that miR-25 was highly expressed both in clinical ovarian cancer samples and cell lines. Down-regulation of miR-25 in ovarian cancer cells induced apoptosis whereas overexpression of miR-25 enhanced cell proliferation. The effects of miR-25 abrogation were partly mediated by the intrinsic apoptosis pathway. Many pro-apoptotic proteins such as Bim, Bax and caspase-3 were up-regulated after transfection. Furthermore, luciferase assays demonstrated that Bim was the direct target of miR-25. Introducing Bim cDNA without 3'UTR abrogated miR-25-induced cell survival. Finally, there was an inverse relationship between Bim and miR-25 expression in ovarian cancer tissues. Taken together, these data indicate that miR-25 directly regulates apoptosis by targeting Bim in ovarian cancer and that miR-25 could be a potential therapeutic target for ovarian cancer intervention.

Chloroplasts divide by binary fission, which is accomplished by the simultaneous constriction of the FtsZ ring on the stromal side of the inner envelope membrane, and the ARC5 ring on the cytosolic side of the outer envelope membrane. The two rings are connected and coordinated mainly by the interaction between the inner envelope membrane protein ARC6 and the outer envelope membrane protein PDV2 in the intermembrane space. The underlying mechanism of this coordination is unclear to date. Here, we solved the crystal structure of the intermembrane space region of the ARC6-PDV2 complex. The results indicated that PDV2 inserts its carboxy terminus into a pocket formed in ARC6, and this interaction further induces the dimerization of the intermembrane space regions of two ARC6 molecules. A pdv2 mutant attenuating PDV2-induced ARC6 dimerization showed abnormal morphology of ARC6 rings and compromised chloroplast division in plant cells. Together, our data reveal that PDV2-induced dimerization of ARC6 plays a critical role in chloroplast division and provide insights into the coordination mechanism of the internal and external plastid division machineries.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck, and improving the efficiency of its diagnosis and treatment strategies is an important goal. With the development of the combination of artificial intelligence (AI) technology and medical imaging in recent years, an increasing number of studies have been conducted on image analysis of NPC using AI tools, especially radiomics and artificial neural network methods. In this review, we present a comprehensive overview of NPC imaging research based on radiomics and deep learning. These studies depict a promising prospect for the diagnosis and treatment of NPC. The deficiencies of the current studies and the potential of radiomics and deep learning for NPC imaging are discussed. We conclude that future research should establish a large-scale labelled dataset of NPC images and that studies focused on screening for NPC using AI are necessary.

Introduction Oridonin, which is isolated from the Chinese herb Rabdosia rubescens, has been reported to exhibit an anti-tumorous effect on different cancers. In this study, we investigated the molecular mechanism by which oridonin suppresses human ovarian cancer. Material and methods The inhibition of oridonin on cell proliferation was assessed by CCK8 assay. Cell cycle and apoptosis were analyzed by flow cytometry, staining with propidium iodide (PI) or annexin-V/PI respectively. The metastasis rate was evaluated using a transwell migration assay. The expression of metastasis-associated genes and mTOR pathway related genes were detected by western blot. Results We demonstrated that oridonin suppressed the proliferation and blocked the cell cycle in G1/S phage and induced apoptosis in SKOV3 and A2780 cells ( p < 0.01). We further found that the mTOR signaling pathway was suppressed by the treatment with oridonin, and the activation of the mTOR pathway attenuated the anti-tumorous effect of oridonin in human ovarian cancer cells, suggesting that the mTOR pathway was involved in the anti-tumorous process of oridonin. Additionally, the activation of the mTOR pathway by an exogenous activator reduced the expression level of FOXP3 ( p < 0.01), thus providing evidence that FOXP3 is a factor that is necessary for the anti-tumorous effect of oridonin, and is negatively regulated by the mTOR pathway. Conclusions These results suggested that oridonin suppressed the mTOR signaling pathway, up-regulated the FOXP3 level, and inhibited metastasis of human ovarian cancer cells.

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

Multidrug resistance is a major limitation for microtubule-binding agents in cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl-5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity against multidrug-resistant cell lines and its antitumor efficacy in animal models. IMB5046 disrupted microtubule structures in cells and inhibited purified tubulin polymerization in vitro. It bound to the colchicine pocket of tubulin. IMB5046 displayed potent cytotoxicity against multiple tumor cell lines with an IC50 range of 0.037–0.426 μM. Notably, several multidrug-resistant cell lines which were resistant to colchicine, vincristine and paclitaxel remained sensitive to IMB5046. IMB5046 was not a P-glycoprotein substrate. IMB5046 blocked cell cycle at G2/M phase and induced cell apoptosis. Microarray assay indicated that the differentially expressed genes after IMB5046 treatment were highly related to immune system, cell death and cancer. In a mouse xenograft model IMB5046 inhibited the growth of human lung tumor xenograft by 83% at a well-tolerated dose. It is concluded that IMB5046 is a tubulin polymerization inhibitor with novel chemical structure and can overcome multidrug resistance. It is a promising lead compound for cancer chemotherapy, especially for treatment of multidrug-resistant tumors.

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