Tieliang Ma

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.

PKM2 gene regulates the behavior of pancreatic cancer cells via mitogen-activated protein kinase pathways.

The aim of the current study was to investigate the effect of the PKM2 gene on the proliferation, invasion, migration and apoptosis of Panc‑1 and Sw1990 pancreatic cancer cells via its interaction with the mitogen‑activated protein kinases (MAPKs) signaling pathways. The expression levels of PKM2 protein in pancreatic cancer cells and the corresponding normal tissues was determined with western blot analysis. Immunohistochemical analysis of PKM2 expression was carried out in paraffin‑embedded sections of pancreatic cancer tissue. Two human pancreatic cancer cell lines were cultured in vitro, and a small interfering RNA (siRNA) was designed for the PKM2 gene and transfected into the cells. Cell proliferation was measured via an MTT assay, cell migration and invasion was measured via Transwell® chambers, and the effect of PKM2 on apoptosis was detected from B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein expression levels. Protein expression levels of the MAPK pathway proteins extracellular signal‑regulated kinase 1/2 (ERK1/2), p38 and c‑Jun N‑terminal kinase (JNK) and their phosphorylated forms were measured via western blot analysis. The expression level of PKM2 was significantly upregulated in the pancreatic cancer tissue compared with that of the corresponding normal tissue. Downregulation of PKM2 expression reduced the proliferation, migration and invasion of pancreatic cancer cell lines, while increasing the levels of apoptosis. Additionally, the expression levels of the phosphorylated‑(p‑)ERK1/2 and p‑p38 of the MAPK pathway in the PKM2 siRNA groups were markedly downregulated compared with those of the controls; however, the expression levels of ERK1/2, p38, JNK, p‑p38 and p‑JNK had no significantly changes compared with those of the control groups. In summary, the PKM2 gene has an important role in the proliferation, invasion, migration and apoptosis of Panc‑1 and Sw1990 pancreatic cancer cells, which may be associated with the expression of ERK1/2 and p38 of the MAPK signaling cascade.

Multifunctional nanocomposite based on halloysite nanotubes for efficient luminescent bioimaging and magnetic resonance imaging

A novel multifunctional halloysite nanotube (HNT)-based Fe3O4@HNT-polyethyleneimine-Tip-Eu(dibenzoylmethane)3 nanocomposite (Fe-HNT-Eu NC) with both photoluminescent and magnetic properties was fabricated by a simple one-step hydrothermal process combined with the coupling grafting method, which exhibited high suspension stability and excellent photophysical behavior. The as-prepared multifunctional Fe-HNT-Eu NC was characterized using various techniques. The results of cell viability assay, cell morphological observation, and in vivo toxicity assay indicated that the NC exhibited excellent biocompatibility over the studied concentration range, suggesting that the obtained Fe-HNT-Eu NC was a suitable material for bioimaging and biological applications in human hepatic adenocarcinoma cells. Furthermore, the biocompatible Fe-HNT-Eu NC displayed superparamagnetic behavior with high saturation magnetization and also functioned as a magnetic resonance imaging (MRI) contrast agent in vitro and in vivo. The results of the MRI tests indicated that the Fe-HNT-Eu NC can significantly decrease the T2 signal intensity values of the normal liver tissue and thus make the boundary between the normal liver and transplanted cancer more distinct, thus effectively improving the diagnosis effect of cancers.

Decreased left hippocampal volumes in parents with or without posttraumatic stress disorder who lost their only child in China.

BACKGROUND Limbic structural changes have been found in people with post-traumatic stress disorder (PTSD). However, the results were controversial, and no study has examined the hippocampal and amygdala volume changes in parents with or without PTSD who had lost their only child and could no longer conceive in China. METHODS Hippocampal and amygdala volumes of 57 parents with PTSD (PTSD+), 11 trauma-exposed parents without PTSD (PTSD-) and 39 non-traumatized controls were examined using magnetic resonance imaging. Correlations of the volumes with the time since trauma, Clinician-Administered PTSD Scale (CAPS) scores, age, gender and intracranial volume (ICV) were investigated in the PTSD+ group. RESULTS left hippocampal volumes were significantly smaller in the PTSD+ and PTSD- groups than in the controls, but there were no significant differences between the PTSD+ and PTSD- groups. Furthermore, there was no significant difference in the right hippocampus or bilateral amygdala volumes. Additionally, the hippocampal and amygdala volumes showed no correlation with the time since trauma, CAPS score and gender, whereas the left hippocampal volumes were correlated with ICV, and the bilateral amygdala volumes were correlated with ICV and age in the PTSD+ group. LIMITATIONS The PTSD- group included only 11 participants. CONCLUSIONS left hippocampal volumes decreased in parents who lost their only child, with or without PTSD. Our results suggest a potentially unique role of the trauma of losing an only child, which is extremely painful and may induce a decrease in the left hippocampal volume independent of PTSD effects.

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.

A novel visual ratiometric fluorescent sensing platform for highly-sensitive visual detection of tetracyclines by a lanthanide- functionalized palygorskite nanomaterial

A palygorskite (Pal)-based ratiometric fluorescent nanoprobe is designed in order to establish a real time, on-site visual, and highly sensitive detection method for tetracyclines (TCs). The nanoprobe comprises the green emissive dye molecules embedded in the natural Pal, which serve as the internal reference signal. The potential red-emissive seed-europium (Eu3+) ions are covalently bound on the surface of modified Pal, and they can act as the specific recognition element. The emission intensity of Eu3+ ions significantly increases upon TC addition. The nanoprobe fluorescence changes from green to yellow, orange, or red, thereby accomplishing the visual ratiometric fluorescent detection. This nanoprobe exhibits a high sensitivity with a detection limit of 7.1nM and an excellent selectivity in monitoring the levels of TCs in milk samples. In addition, this nanoprobe is useful for quantitative determination of TCs, and it is not affected with intensity fluctuations due to instrumental or environmental factors. The nanoprobe-immobilized test paper realizes real-time TCs analysis by using a smartphone with an easy-to-access color-scanning APP as the detection platform. Moreover, the reported construction of visual ratiometric detection system follows the sustainable development idea, that is, from nature, for nature, and into the nature.

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.

The atrophy and laterality of the hippocampal subfields in parents with or without posttraumatic stress disorder who lost their only child in China

Investigating hippocampal subfields may provide new and important insights into the pathophysiology of posttraumatic stress disorder (PTSD). However, no study has examined the hippocampal subfield volume changes in parents with or without PTSD who had lost their only child and could no longer conceive in China. Fifty-seven parents with PTSD (PTSD+), 11 trauma-exposed parents without PTSD (PTSD−), and 39 non-traumatized controls were recruited to examine the hippocampal subfield volumes using magnetic resonance imaging. Correlations of the volumes with the time since trauma and Clinician-Administered PTSD Scale (CAPS) scores were investigated in the PTSD+ group. The volumes of the bilateral cornu ammonis (CA) 2–3, CA4–dentate gyrus (DG), and left subiculum were significantly smaller in the PTSD+ and PTSD− groups than in the controls, but there were no significant differences between the PTSD+ and PTSD− groups. Additionally, the left CA2–3 and CA4–DG volumes reduced more than those on the right side in the PTSD+ and PTSD− groups. The subfield volumes were not related to the time since trauma and the CAPS scores in the PTSD+ group. In conclusion, hippocampal subfield volumes decreased in parents who lost their only child with or without PTSD, and the volumetric reduction may be independent of PTSD and trauma-related. Moreover, the hippocampal volume deficits showed laterality that the left side was affected more than the right, and the hippocampal subfields may show differential vulnerabilities to trauma/PTSD, with the CA2–3 and CA4–DG subfields more sensitive than others.