Jing Xie

Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice

Our objective was to investigate the pathogenesis pathways of idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) induced animal models of experimental lung fibrosis were used. CHIP assay was executed to find the link between Smad3 and IL-31, and the expressions of TGF-β1, Smad3, IL-31 and STAT1 were detected to find whether they were similar with each other. We found that in the early injury or inflammation of the animal model, BLM promoted the development of inflammation, leading to severe pulmonary fibrosis. Then the expression of TGF-β1 and Smad3 increased. Activated Smad3 bound to the IL-31 promoter region, followed by the activation of JAK-STAT pathways. The inhibitor of TGF-β1 receptor decreased the IL-31 expression and knocking-down of IL-31 also decreased the STAT1 expression. We conclude that there is a pathway of pathogenesis in BLM-induced mouse model that involves the TGF-β, IL-31 and JAKs/STATs pathway.

Anticancer Activity and DNA‐Binding Investigations of the Cu(II) and Ni(II) Complexes with Coumarin Derivative

Two new copper(II) (2) and nickel(II) (3) complexes with a new coumarin derivative have been synthesized and structurally characterized. The DNA‐binding activities of the two complexes have been investigated by spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis, and viscosity measurements. The results indicate that the two complexes, especially the complex 2, can strongly bind to calf‐thymus DNA (CT‐–DNA). The intrinsic binding constants Kb of the complexes with CT‐DNA are 2.99 × 105 and 0.61 × 105 for 2 and 3, respectively. Comparative cytotoxic activities of the two complexes are also determined by MTT assay. The results show that the drugs designed here have significant cytotoxic activity against the human hepatic (HepG2), human promyelocytic leukemia (HL60), and human prostate (PC3) cell lines. Cell apoptosis was detected by Annexin V/PI flow cytometry, and the results show that the two copper complexes can induce apoptosis of the three human tumor cells. In conclusions, the two complexes show considerable cytotoxic activity against the three human cancer and induce apoptosis of the threes.

Ternary Dinuclear Copper(II) Complexes of a Reduced Schiff Base Ligand with Diimine Coligands: DNA Binding, Cytotoxic Cell Apoptosis, and Apoptotic Mechanism.

A serial of mixed‐ligand Cu(II) complexes of the type [Cu(phens)(H2PDILeu)]H2O (1‐4) containing phens as 2,2′‐bipyridyl (bpy, 1), 1,10‐phenanthroline (phen, 2), dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq, 3), and dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz, 4) have been isolated and characterized. The interaction of the complexes with calf‐thymus DNA has been explored by physical methods to propose modes of DNA binding of the complexes, which indicate that 4 interacts with DNA more strongly than all of the other complexes through intercalation interaction. Furthermore, cell apoptosis was detected by AnnexinV/PI flow cytometry and TUNEL assay and by Western blotting to detect the protein expression of p53, Bax, and Bcl‐2. All the three copper complexes can effectively induce apoptosis of the three human tumor cells, which was accompanied with upregulation of the expression of p53 and Bax, while Bcl‐2 decreased.

DNA damage in peripheral blood lymphocytes from patients with OSAHS

PurposeObstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by intermittent hypoxia during sleep time, followed by oxidative stress. Hypoxia-induced oxidative stress can lead to DNA damage, which is related to chromosome aberrations and micronuclei. The purpose of this study is to investigate the level of DNA damage in peripheral blood of patients with OSAHS.MethodsThirty patients with OSAHS diagnosed by polysomnography and 28 healthy volunteers were assessed by the Epworth sleepiness scale. The levels of DNA damage were investigated through the cytokinesis-blocked micronucleus assay.ResultsIn the group of patients with OSAHS, the mean frequency of binucleated cells with micronuclei were significantly higher than that in the control group (P < 0.01), and the frequency of micronuclei among the patients in mild, moderate, and severe stages differed significantly (P < 0.05). The mean frequency of nucleoplasmic bridge in OSAHS group was also higher than that in the control group (P < 0.05). Nasal continuous positive airway pressure treatment decreased the frequencies of binucleated cells with micronuclei, nucleoplasmic bridge, and nuclear buds.ConclusionsOxidative DNA damage increased in peripheral blood lymphocytes of OSAHS patients. It may be related to oxidative stress induced by intermittent hypoxia and may be involved in the pathogenesis of cardiovascular and other target organ injuries.

Design and synthesis of novel N(4)-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents

A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, 1H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.