Design, synthesis and biological evaluations of niclosamide analogues against SARS-CoV-2.

Niclosamide, a widely-used anthelmintic drug, inhibits SARS-CoV-2 virus entry through TMEM16F inhibition and replication through autophagy induction, but the relatively high cytotoxicity and poor oral bioavailability limited its application. We synthesized 22 niclosamide analogues of which compound 5 was found to exhibit the best anti-SARS-CoV-2 efficacy (IC = 0.057 μ M) and compounds 6, 10, and 11 (IC = 0.

Proteomic analysis of ionizing radiation-induced proteins at the subcellular level.

Irradiation induces a series of liver diseases. However the molecular mechanisms involving in the process of liver diseases induced by irradiation are still unclear. Subcellular proteomics provides a method to understand regional differences in protein expression levels.

In vitro and in vivo protection against the highly pathogenic H5N1 influenza virus by an antisense phosphorothioate oligonucleotide.

Background: Current vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of a novel antisense oligonucleotide (named IV-AS), which is specific for the 5'-terminal conserved sequence found in all eight viral RNA segments of influenza A virus.

Methods: The activity of IV-AS was monitored both in vitro, in Madin-Darby canine kidney (MDCK) cells, and in vivo using a mouse model.

Inhibition of hepatocellular carcinoma growth by antisense oligonucleotides to type I insulin-like growth factor receptor in vitro and in an orthotopic model.

Aim: The type I insulin-like growth factor receptor (IGF-IR) is overexpressed in many tumors including human hepatocellular carcinoma (HCC). It is a critical signaling molecule for tumor cell proliferation and survival. In the present study, IGF-IR expression was down-regulated by phosphorothioate antisense oligonucleotides (AS[S]ODN) to evaluate their specific effects on growth of hepatoma cells in vitro and in vivo.

SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity.

The tumor suppressor p53-related p73 shares significant amino-acid sequence identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and activates p53-responsive target genes and induces apoptosis. Moreover, SIRT1 binds to p53 while repressing the expression of their target genes.

Microarray analysis of differentially expressed genes in mouse bone marrow tissues after ionizing radiation.

Purpose: To identify differentially expressed genes in mouse bone marrow involved in radiation-induced injury.

Materials And Methods: Microarray analysis was used to identify the differentially expressed genes and other techniques, e.g.

[Screening and their anti-tumor activity of antisense oligodeoxynucleotides targeting KDR mRNA in breast cancer MCF-7 cells].

Objective: To screen the antisense oligodeoxynucleotides (asONs) which could hybridize with KDR (kinase insert domain-containing receptor) mRNA in an effective and specific way and to explore their anti-tumor effects on breast cancer MCF-7 cell line in vitro.

Methods: The asONs were firstly selected using oligodeoxynucleotides library hybridization or computer prediction, then their hybridization ability with KDR mRNA was further tested with oligonucleotide microarray. The asONs with strong hybridization intensity were selected.

Identification of differentially expressed genes contributing to radioresistance in lung cancer cells using microarray analysis.

Radiotherapy has played a key role in the control of tumor growth in many cancer patients. It is usually difficult to determine what fraction of the tumor cell population is radioresistant after a course of radiotherapy. The response of tumor cells to radiation is believed to be accompanied by complex changes in the gene expression pattern.

Inhibition of tumor growth and metastasis with antisense oligonucleotides (Cantide) targeting hTERT in an in situ human hepatocellular carcinoma model.

Aim: To evaluate the in vivo antitumor effects of Cantide and the combined effect with 5-fluorouracil.

Methods: An in situ human hepatocellular carcinoma model was established in mice livers orthotopically. Drugs were administered intravenously and tumor sizes were monitored with calipers.

Effective siRNA targets screening for human telomerase reverse transcriptase.

Aim: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.

Methods: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4 sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly.

Combined effects of Cantide and chemotherapeutic drugs on inhibition of tumor cells' growth in vitro and in vivo.

Aim: To investigate the combination effect of hTERT antisense oligonucleotide "Cantide" and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo.

Methods: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d.

Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation of DU-145 cells.

Aim: To investigate the effect of antisense oligodeoxynucleotides (ASODN) targeting Pim-2 on cell proliferation of DU-145 cells.

Methods: Three ASODN targeting Pim-2 were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed using an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay.