Apoptosis Activation in Thyroid Cancer Cells by Jatrorrhizine-Platinum(II) Complex via Downregulation of PI3K/AKT/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Thyroid cancer, which is the most common endocrine cancer, has shown a drastic increase in incidence globally over the past decade. The present study investigated the thyroid cancer-inhibitory potential of jatrorrhizine-platinum(II) complex (JR-P(II) in vitro and in vivo. MATERIAL AND METHODS The JR-P(II)-mediated cytotoxicity in thyroid carcinoma cells was determined by using MTT assay. Assessment of acetylated histones, tubulin, and DNA repair proteins was made by Western blot assays. Flow cytometry was used for apoptosis and ROS accumulation measurement. RESULTS The JR-P(II) suppressed proliferative capacity of SW1736, BHP7-13, and 8305C cells. JR-P(II) treatment markedly promoted expression of acetylated histone H3, H4, and tubulin in a dose-dependent manner. Treatment with JR-P(II) significantly elevated the proportion of cells in sub-G1 and promoted cleaved caspase-3 and -9. In JR-P(II)-treated cells, DCFH-DA fluorescence was much higher relative to control cells. The JR-P(II) treatment consistently suppressed expression of pS6, p-ERK1/2, p-4E-BP1, and p-AKT, and increased p-H2AX expression and suppressed KU70 and KU80 protein levels. The level of RAD51 was repressed in JR-P(II)-treated cells. JR-P(II) administration in mice caused no significant change in body weight, and it inhibited SW1736 tumor growth in mice. CONCLUSIONS The JR-P(II) induced cytotoxicity in thyroid cancer cells by inhibiting the mechanism responsible for repair of double-stranded DNA. The in vivo data also revealed that JR-P(II) effectively inhibits thyroid tumor growth by inducing DNA damage. Thus, our results suggest that further evaluation of JR-P(II) as a therapeutic candidate for thyroid cancer is warranted.

Recent advances in metal-organic frameworks for gas adsorption/separation.

The unique structural advantage of metal-organic frameworks (MOFs) determines the great prospect and developability in gas adsorption and separation. Both ligand design and microporous engineering based on crystal structure are significant lever for coping with new application exploration and requirements. Focusing on the designable pore and modifiable frameworks of MOFs, this review discussed the recent advances in the field of gas adsorption and separation, and analyzed the host-guest interaction, structure-performance relations, and the adsorption/separation mechanism from ligand design, skeleton optimization, metal node regulation, and active sites construction. Based on the function-oriented perspective, we summarized the main research recently, and made an outlook based on the focus of microporous MOFs that require further attention in the structure design and industrial application.

2D coordination polymer-derived CoSe2-NiSe2/CN nanosheets: the dual-phase synergistic effect and ultrathin structure to enhance the hydrogen evolution reaction.

The evolution of cost-effective hydrogen evolution reaction (HER) electrocatalysts is of great significance for the development of clean energy. Exploring effective synthesis strategies to optimize the performance of non-noble metal electrocatalysts has always attracted our attention. Herein, ultrathin coordination polymers were used as precursors to controllably synthesize two-dimensional (2D) ultrathin dual-phase transition metal selenide (TMSs)/carbon-nitrogen (CN) composites (CoSe2-NiSe2/CN) by a two-step method (first a low temperature hydrothermal method for selenization, and then high temperature calcination selenization). Benefiting from its large specific surface area (49 m2 g-1), abundant catalytically active sites and synergistic effects, CoSe2-NiSe2/CN can significantly enhance the HER catalytic activity and exhibits good electrocatalytic activity with an overpotential of 150 mV at -10 mA cm-2, and a small Tafel slope of 42 mV dec-1 in an acidic electrolyte for the HER. This work provides a new strategy for optimizing the HER catalytic activity of TMSs by preparing 2D ultrathin dual-phase TMS composite materials.

Optimizing zirconium metal-organic frameworks through steric tuning for efficient removal of Cr2O72.

A ligand with a flexible conformation can be obtained by modifying functional groups. We modified H4DCBA with -CH3/-CF3 groups to construct three Zr-MOFs; the torsion of the central benzene ring changes the topologies. The three Zr-MOFs showed high adsorption rates for Cr2O72-, and the CF3-functional groups enhanced the adsorption capacity of UPC-49 for Cr2O72-.

Clinicopathological and genomic features of breast mucinous carcinoma.

INTRODUCTION: Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood. MATERIALS AND METHODS: 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis. RESULTS: MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P < 0.001). However, after adjusting for clinicopathological factors, survival advantage of MC disappeared. In terms of genomic features of MC, representative upregulated genes of MC in transcriptomic level were MUC2, TFF1 and CARTPT. Upregulated pathways of MC included neurotransmitter-related pathways. Moreover, MC was featured by the amplification of 6p25.2, 6q12 and 11q12.3. CONCLUSION: MC is a distinct histological subtype compared with IDC in terms of clinicopathological characteristics and genomic features. Further investigation need to be conducted to explore the formation of this specific histological subtype.

Two series of Ln-MOFs by solvent induced self-assembly demonstrating the rapid selective sensing of Mg2+ and Fe3+ cations.

Two series of lanthanide-based metal-organic frameworks, namely {[Ln(BIPA-TC)0.5(DMA)2(NO3)]·DMA·H2O}n (1-Ln, Ln = Eu, Dy, Sm, Nd) and {[Ln2(BIPA-TC)1.5(DMA)3(H2O)2]·2DMA·2H2O}n (2-Ln, Ln = Eu, Dy, Sm, Nd), were successfully constructed via a solvent regulation strategy based on a π-electron rich tetra-carboxylate ligand (H4BIPA-TC). 1-Ln shows a 4-connected lvt topology with the point symbol of {42·84}, but 2-Ln displays a new 4,4,6-connected wxk1 topology with the point symbol of {43·83}4{46·66·83}2{86}. The solid-state luminescence property and the microporous nature of Eu-MOFs (1-Eu and 2-Eu) indicate that they can potentially be used as luminescent sensors. Fluorescence measurements indicate that Fe3+ exhibits the quenching effect for 1-Eu with the quenching efficiency of 93.1%. 2-Eu is the first MOF sensor for Mg2+ with the lowest detection limit of 1.53 × 10-10 mol L-1 and displays good recyclable capability. Simultaneously, in the presence of other metal ions (Ca2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Pd2+, Al3+, Cr3+and Fe3+), 2-Eu can maintain the selective sensing of Mg2+, indicating its potential for Mg2+ turn-on sensing.

The Histone H3 Lysine 4 Presenter WDR5 as an Oncogenic Protein and Novel Epigenetic Target in Cancer.

The histone H3 lysine 4 (H3K4) presenter WDR5 forms protein complexes with H3K4 methyltransferases MLL1-MLL4 and binding partner proteins including RBBP5, ASH2L, and DPY30, and plays a key role in histone H3K4 trimethylation, chromatin remodeling, transcriptional activation of target genes, normal biology, and diseases such as MLL-rearranged leukemia. By forming protein complexes with other proteins such as Myc, WDR5 induces transcriptional activation of key oncogenes, tumor cell cycle progression, DNA replication, cell proliferation, survival, tumor initiation, progression, invasion, and metastasis of cancer of a variety of organ origins. Several small molecule MLL/WDR5 protein-protein interaction inhibitors, such as MM-401, MM-589, WDR5-0103, Piribedil, and OICR-9429, have been confirmed to reduce H3K4 trimethylation, oncogenic gene expression, cell cycle progression, cancer cell proliferation, survival and resistance to chemotherapy without general toxicity to normal cells. Derivatives of the MLL/WDR5 interaction inhibitors with improved pharmacokinetic properties and in vivo bioavailability are expected to have the potential to be trialed in cancer patients.