Fused metallacyclopropenes from alkynylphenols.

Metallacycloprop-1-enes can be constructed from coordinated alkynes. In this work, we report a convenient synthesis of fused osmacyclopropene complexes 1 and 3 from OsCl2(PPh3)3 and alkynylphenols. Paramagnetic alkyne-coordinated phenolate complexes 2 were obtained as the key intermediates for the formation of osmacyclopropenes, demonstrating selective CC activation under different conditions.

Correction: A molecularly imprinted antibiotic receptor on magnetic nanotubes for the detection and removal of environmental oxytetracycline.

Correction for 'A molecularly imprinted antibiotic receptor on magnetic nanotubes for the detection and removal of environmental oxytetracycline' by Jixiang Wang et al., J. Mater. Chem. B, 2022, 10, 6777-6783, https://doi.org/10.1039/D2TB00497F.

Anticancer Effects of Amlodipine Alone or in Combination With Gefitinib in Non-Small Cell Lung Cancer.

Amlodipine is a Ca2+ channel blocker commonly used to cardiovascular diseases such as hypertension and angina; however, its anticancer effects in lung cancer A549 cells remain unknown. In the present study, we explored the antitumor effects and molecular mechanisms underlying the action of amlodipine in non-small cell lung cancer (NSCLC) A549 cells in vitro and in vivo. We observed that amlodipine suppressed the proliferation of A549 lung cancer cells by arresting the tumor cell cycle. Mechanistically, our results revealed that amlodipine could attenuate the phosphoinositide 3 kinase (PI3K)/Akt and Raf/MEK/extracellular signal-regulated kinase (ERK) pathways through epidermal growth factor receptor (EGFR) and modulated cell cycle-related proteins such as cyclin D1, p-Rb, p27, and p21. Subsequently, amlodipine combined with gefitinib could synergistically inhibit cell proliferation by arresting the cell cycle. Moreover, amlodipine combined with gefitinib effectively attenuated the growth of A549 lung cancer xenografts when compared with monotherapy, affording an excellent therapeutic effect. Collectively, our results indicate that amlodipine alone or combined with the novel anticancer drug gefitinib might be a potential therapeutic strategy for NSCLC patients with wild-type EGFR.

A molecularly imprinted antibiotic receptor on magnetic nanotubes for the detection and removal of environmental oxytetracycline.

The detection and elimination of antibiotic contaminants, such as oxytetracycline (OTC), a broad-spectrum tetracycline antibiotic, would be of help in efficient environmental monitoring, agriculture and food safety tests. Nevertheless, currently available methodologies, which mostly rely on the chromatographic separation of OTC, suffer from low sensitivity and complicated processes. Thus, we report here on the design and synthesis of a fluorescent sensor based on molecularly imprinted magnetic halloysite nanotubes (referred to as MHNTs@FMIPs) for the effective detection and purification of OTC in actual environmental samples. The fluorescence of the MHNTs@FMIPs was quenched obviously upon loading with OTC, covering a linear concentration range of 10-300 nM with a limit of detection (LOD) as low as 8.1 nM. The imprinting factor is 4.47, indicating an excellent specificity. Furthermore, the MHNTs@FMIPs can be applied to the quantitative detection of OTC (5 cycles of 300 nM) in aquaculture wastewater and Yangtze River water, demonstrating their immense application potential.

Targeting c-Jun in A549 Cancer Cells Exhibits Antiangiogenic Activity In Vitro and In Vivo Through Exosome/miRNA-494-3p/PTEN Signal Pathway.

The oncogene c-Jun is activated by Jun N-terminal kinase (JNK). Exosomes are nanometer-sized membrane vesicles released from a variety of cell types, and are essential for cell-to-cell communication. By using specific JNK inhibitor SP600125 or CRISPR/Cas9 to delete c-Jun, we found that exosomes from SP600125-treated A549 cancer cells (Exo-SP) or from c-Jun-KO-A549 cells (Exo-c-Jun-KO) dramatically inhibited tube formation of HUVECs. And the miR-494 levels in SP600125 treated or c-Jun-KO A549 cells, Exo-SP or Exo-c-Jun-KO, and HUVECs treated with Exo-SP or Exo-c-Jun-KO were significantly decreased. Meanwhile, Exo-SP and Exo-c-Jun-KO enhanced expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Addition of miR-494 agomir in Exo-c-Jun-KO treated HUVECs inhibited PTEN expression and promoted tube formation, suggesting the target of miR-494 might be PTEN in HUVECs. Moreover, A549 tumor xenograft model and Matrigel plug assay demonstrated that Exo-c-Jun-KO attenuated tumor growth and angiogenesis through reducing miR-494. Taken together, inhibition of c-Jun in A549 cancer cells exhibited antiangiogenic activity in vitro and in vivo through exosome/miRNA-494-3p/PTEN signal pathway.

STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

Inhibitory effect of taxifolin on mast cell activation and mast cell-mediated allergic inflammatory response.

The aim of the present study is to investigate the anti-inflammatory and anti-allergic effects of taxifolin on mast cells and mast cell-mediated allergic reaction. We assessed the effect of taxifolin on the activation of bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells induced by immunoglobulin E (IgE)/antigen (Ag), and the activation of human mast cell line (HMC-1) induced by PMA plus A23187. Taxifolin inhibited degranulation, generation of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) through blocking intracellular Ca2+ mobilization, phosphorylation of phospholipase Cγ (PLCγ) and mitogen-activated protein kinases (MAPKs), translocation of cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO), and Akt/IKK/NF-κB pathway, in BMMC cells. Furthermore, taxifolin suppressed phosphorylation of Syk, but without effect on Fyn and Lyn. Taxifolin also inhibited activation of RBL-2H3 and HMC-1 cells via Akt/IKK/NF-κB and MAPKs/cPLA2 signal pathway. Treatment with taxifolin attenuated the mast cell-mediated passive cutaneous anaphylaxis (PCA) reaction. Our results suggest that taxifolin might become a potential drug candidate for the treatment of allergic and inflammatory diseases.

Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction.

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

[Methylation status of JunB and CDH13 gene promoter in CD34(+)CD38(-) chronic myelogenous leukemia cells].

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. The expressions of JunB and CDH13 (cadherin-13) gene as tumor suppressor gene were inactivated by promoter methylation in CML patients. This study was purposed to investigate the methylation difference of JunB and CDH13 gene promoter and the expression levels of JunB and CDH13 gene in CD34(+)CD38(-) cells in CML patients vs normal individuals. CD34(+)CD38(-) cells from 8 cases of CML and 5 normal individuals were selected by flow cytometry. The methylation status of JunB and CDH13 genes were detected by MS-PCR in selected CD34(+)CD38(-) cells. The expression levels of JunB and CDH13 gene was detected with real time polymerase chain reaction (RT-PCR). The results showed that no methylation of JunB and CDH13 gene was detected in CD34(+)CD38(-) cells of 5 normal individuals. Methylations of JunB and CDH13 promoter were found in 87.5% (7/8) and 50% (4/8) CML CD34(+)CD38(-) cells, percentages of which were significantly higher than those in normal individuals. The difference was statistically significant (p < 0.05). The relative expression levels of JunB and CDH13 mRNA in CD34(+)CD38(-) cells of CML patients were significantly lower than those in normal individuals (2(-DeltaDeltaCT) were 1/5.21 and 1/10.63 respectively). It is concluded that the high methylation of JunB and CDH13 gene promoter occurs in CD34(+)CD38(-) cells of CML patients, their mRNA expression level is significantly lower, thus the methylation of JunB and CDH13 gene promoter probably plays a role in the pathogenesis of CML and may have clinical significance in predicting prognosis of CML.

Berberine inhibits SDF-1-induced AML cells and leukemic stem cells migration via regulation of SDF-1 level in bone marrow stromal cells.

Berberine plays a prominent role on the control of tumor cell invasion and migration. SDF-1 is a homeostatic chemokine that signals through CXCR4 which is expressed by hematopoietic tumor cells. The SDF-1/CXCR4 axis is involved in the migration process of leukemic cells. In this study, we investigated the effects of berberine on the SDF-1-induced HL-60 cells, primary acute myeloid leukemia (AML) cells and leukemic stem cells (LSCs) migration. Transwell migration chambers (8 microm) were used to assess the role of berberine on leukemic cell migration; Flow cytometry was used to analyze the role of berberine on the CXCR4 expression; SDF-1 protein level secreted by bone marrow stromal cells (BMSCs) was evaluated by ELISA. Results demonstrated that berberine could partly inhibit SDF-1-induced AML cells as well as LSCs migration. Berberine could reduce SDF-1 protein level secreted by BMSCs in the microenvironment but not affect CXCR4 expression on HL-60 cell membrane, and we hypothesized that berberine could inhibit AML cells migration partly by reducing the secreting of SDF-1 by BMSCs and inhibiting HERG1 K(+) channels of leukemic cells. Therefore, it is speculated that berberine might be a potentially effective agent for prevention of leukemia.