Oncogenic roles and drug target of CXCR4/CXCL12 axis in lung cancer and cancer stem cell.

Although the great progress has been made in diagnosis and therapeutic in lung cancer, it induces the most cancer death worldwide in both males and females. Chemokines, which have chemotactic abilities, contain up to 50 family members. By binding to G protein-coupled receptors (GPCR), holding seven-transmembrane domain, they function in immune cell trafficking and regulation of cell proliferation, differentiation, activation, and migration, homing under both physiologic and pathologic conditions.

Relationships between serum Omentin-1 levels and bone mineral density in older men with osteoporosis.

Objective: To investigate the correlation between serum Omentin-1 levels and the presence of osteoporosis in older men.

Methods: Serum Omentin-1, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 45 older men with osteoporosis or 45 older men without osteoporosis (65-70 years old).

Results: Omentin-1 levels were increased in older men with osteoporosis, and the differences remained significant after controlling for fat mass.

SENP‑1 enhances hypoxia‑induced proliferation of rat pulmonary artery smooth muscle cells by regulating hypoxia‑inducible factor‑1α.

Hypoxic pulmonary vascular remodeling (HPSR) has an important role in the development of hypoxic pulmonary hypertension. HPSR is predominantly mediated by the proliferation of pulmonary artery smooth muscle cells (PASMCs). Our previous study demonstrated that hypoxia‑inducible factor (HIF)‑1α was able to promote the proliferation of PASMCs.

Bevacizumab induces A549 cell apoptosis through the mechanism of endoplasmic reticulum stress in vitro.

Aims: To observe the effect of bevacizumab on human A549 cells and explore its mechanism.

Methods: After different concentrations (0 μM, 1 μM, 5 μM, 25 μM) of bevacizumab treating in A549 cells, CCK8 assay detect the impact of bevacizumab on A549 cell proliferation and flow cytometry determine the effect of bevacizumab on human A549 cells apoptosis. Real-time PCR and Western blotting detect the changing expression of the target gene (CHOP, caspase-4, IRE1, XBP-1) on mRNA and Protein level.

Increased SUMO-1 expression in response to hypoxia: Interaction with HIF-1α in hypoxic pulmonary hypertension.

Pulmonary hypertension (PH) develops in 30-70% of chronic obstructive pulmonary disease patients and increases morbidity and mortality. The present study aimed to investigate the regulation of small ubiquitin‑related modifier‑1 (SUMO‑1) expression in response to hypoxia. The experiments were carried out in vitro in rat pulmonary arterial smooth muscle cells (PASMCs) and in vivo using a rat hypoxic PH (HPH) model.

A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3).

MicroRNAs (miRNAs) involve in the regulation of a wide range of physiological processes. Recent studies suggested that miRNAs might play a role in osteoclast differentiation. Here, we identify a new miRNA (miR-9718) in primary mouse osteoclasts that promotes osteoclast differentiation by repressing protein inhibitor of activated STAT3 (PIAS3) at the post-transcriptional level.

Methylation of PRDM2, PRDM5 and PRDM16 genes in lung cancer cells.

Aims: To investigate the changes of expression and methylation status of PRDM2, PRDM5, PRDM16 in lung cancer cells after treatment with demethylation agent.

Methods: A549 (lung adenocarcinoma cell line), HTB-182 (lung squamous cell carcinoma cell line) and HBE (normal bronchial cell line) were treated with 5-aza-2dC. The methylation state of PRDM2, PRDM5, PRDM16 was detected by MSP.

MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis.

MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis.

[The expression of hypoxia-inducible factor-1alpha and its hydroxylases in pulmonary arteries of patient with chronic obstructive pulmonary disease].

Objective: To observe the expression of hypoxia-inducible factor-lalpha subunit (HIF-1alpha), HIF prolyl hydroxylase domain-containing protein(PHDs) and factor inhibiting HIF-1(FIH) in pulmonary arteries of patient with chronic obstructive pulmonary disease (COPD).

Methods: Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, 12 had concurrent COPD (COPD group) and 14 without COPD (control group). The ratio of vascular wall area to total vascular area (WA%) and pulmonary artery media thickness (PAMT) was observed, and HIF-1alpha and its hydroxylases(PHD1, PHD2, PHD3, FIH) mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively.

[The expression and possible role of SENP1 in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension].

Objective: To investigate the dynamic expression and role of SENP1 (SUMO-specific proteases-1) in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension (HPH).

Methods: Forty adult male Wistar rats were randomly divided into 5 groups (n = 8), and exposed to normoxia (Control group) or exposed to hypoxia for 3, 7, 14 or 21 d, respectively. The HPH models were established by normobaric intermittent hypoxia.

The role of endoplasmic reticulum stress in emphysema results from cigarette smoke exposure.

Apoptosis is of considerable importance in the pathogenesis of emphysema, and recent studies show that endoplasmic reticulum (ER) stress is involved in emphysema. In our research, we investigated the role of protein kinase RNA (PKR)-like ER kinase (PERK)/ eukaryotic initiation factor 2 alpha (eIF2α) pathway, the CCAAT enhancer-binding protein-homologous protein (CHOP) expression, caspase-12 activation and apoptosis in emphysema results from cigarette smoke (CS) exposure. Expression of phosphorylated-PERK (p-PERK), phospholated-eIF2α (p-eIF2α),CHOP and caspase-12 as well as the apoptosis rate are remarkably increased in rats after exposure to 2 months CS compared with control rats, significantly elevated in rats exposed to 4 months CS over rats exposed only to 2 months CS, and slightly decreased in ex-smoking rats in contrast to rats exposed to 4 months CS.

Heat shock protein 27 and cyclophilin A associate with the pathogenesis of COPD.

Background And Objective: COPD is a global disease characterized by chronic bronchitis and obstructive emphysema. Its pathogenesis is not fully understood. This study aimed to use proteomics to provide new insights into the mechanisms of COPD.

Positive correlation between PPARgamma/PGC-1alpha and gamma-GCS in lungs of rats and patients with chronic obstructive pulmonary disease.

Oxidative stress is one of the major pathogenesis of chronic obstructive pulmonary disease (COPD). gamma-Glutamylcysteine synthetase (gamma-GCS) is one of the paramount antioxidant enzymes in COPD. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated transcription factor, which is activated by specific ligands such as rosiglitazone (RGZ), exerting multiple biological effects.

[The cooperation of OS-9 and PHDs in hypoxia-induced pulmonary hypertension of rats].

Aim: To investigate the dynamic expression of hypoxia-inducible factor 1alpha, PHDs and OS-9 in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.

Methods: SD rats were randomly divided into 5 groups (n = 8) and exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. RT-PCR and in situ hybridization were used to determine the expression of mRNA.

Expression and role of factor inhibiting hypoxia-inducible factor-1 in pulmonary arteries of rat with hypoxia-induced hypertension.

Hypoxia-inducible factor-1alpha subunit (HIF-1alpha) plays a pivotal role during the development of hypoxia-induced pulmonary hypertension (HPH) by transactivating it' target genes. As an oxygen-sensitive attenuator, factor inhibiting HIF-1 (FIH) hydroxylates a conserved asparagine residue within the C-terminal transactivation domain of HIF-1alpha under normoxia and moderate hypoxia. FIH protein is downregulated in response to hypoxia, but its dynamic expression and role during the development of HPH remains unclear.

Hypoxia induces transforming growth factor-beta1 gene expression in the pulmonary artery of rats via hypoxia-inducible factor-1alpha.

The present study was undertaken to investigate the dynamic expression of hypoxia inducible factor-1alpha (HIF-1alpha) and transforming growth factor-beta1 (TGF-beta1) in hypoxia-induced pulmonary hypertension of rats. It was found that mean pulmonary arterial pressure (mPAP) increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia.

[Reciprocal regulation between hypoxia-inducible factor-1alpha and its prolyl hydroxylases in hypoxic pulmonary hypertension rats].

Objective: To investigate the interaction between hypoxia-inducible factors-1alpha subunit (HIF-1alpha) and its three prolyl hydroxylases (PHD1, PHD2 and PHD3) during the development of rat hypoxic pulmonary hypertension.

Methods: Forty male SD rats were randomly divided into 5 groups and exposed to normoxia (C group) or exposed to hypoxia for 3, 7, 14 or 21 d (H(3), H(7), H(14), H(21) group), respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured.

[Effects of Nrf2 on gamma-glutamylcysteine synthase in lung of guinea pigs with bronchial asthma].

Aim: To investigate the effects of Nrf2 (Nuclear-E2 related factor) on gamma-glutamylcysteine synthase (gamma-GCS) in lung of guinea pigs with bronchial asthma.

Methods: 20 adult male guinea pigs were randomly divided into two groups (n = 10): control group (C group) and asthmatic group (A group), asthmatic model was established by ovalbumin intraperitoneal and ovalbumin inhalation. The reactive oxygen piece (ROS), reduced glutathione (GSH), oxidant glutathione (GSSG) and total GSH in lung tissue were examined respectively.

Differential and reciprocal regulation between hypoxia-inducible factor-alpha subunits and their prolyl hydroxylases in pulmonary arteries of rat with hypoxia-induced hypertension.

Hypoxia-inducible factor (HIF)-alpha subunits (HIF-1alpha, HIF-2alpha and HIF-3alpha), which play a pivotal role during the development of hypoxia-induced pulmonary hypertension (HPH), are regulated through post-translational hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD1, PHD2 and PHD3). PHDs could also be regulated by HIF. But differential and reciprocal regulation between HIF-alpha and PHDs during the development of HPH remains unclear.

[Differential expression of the three hypoxia-inducible factor alpha subunits in pulmonary artery of rats with hypoxia-induced pulmonary hypertension].

Objective: To differentiate the expression patterns of all hypoxia-inducible factor alpha (HIF-alpha) subunits (HIF-1alpha, HIF-2alpha and HIF-3alpha) in pulmonary artery of rats undergoing systemic hypoxia.

Methods: Forty male healthy wistar rats were assigned randomly to 5 groups, 8 rats per group, then exposed to hypoxia [O2, (10.0 +/- 0.

[The relationship between the polymorphism of glutamate cysteine ligase modulatory subunit gene and the susceptibility to chronic obstructive pulmonary disease].

Objective: To investigate whether glutamate cysteine ligase modulatory (GCLM) subunit gene polymorphism is associated with susceptibility to chronic obstructive pulmonary disease (COPD), and to study the relationship between polymorphism of GCLM gene with plasma gamma-glutamylcysteine synthetase (gamma-GCS) activity.

Methods: Blood samples of 104 stable phase COPD smokers (COPD group), 124 healthy smokers (C group) and 132 healthy never-smokers (H group) were collected, and then the genotypes of GCLM -588C/T and GCLM -23C/T polymorphism sites were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). The plasma gamma-GCS activity was measured by coupled enzyme procedure.

[The expression of capillary hypoxia-induced factor-alpha and pulmonary artery remodeling in chronic obstructive pulmonary disease].

Objective: To observe the expression of hypoxia-inducible factor-alpha (HIF-1alpha, HIF-2alpha, HIF-3alpha) and pulmonary vascular remodeling in pulmonary arteries of patients with chronic obstructive pulmonary disease (COPD).

Methods: Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, of whom 12 had concurrent COPD and 10 without COPD. Pulmonary vascular remodeling was observed with optical microscope, and HIF-alpha mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively.

Transforming growth factor-beta1 induces transdifferentiation of fibroblasts into myofibroblasts in hypoxic pulmonary vascular remodeling.

The muscularization of non-muscular pulmonary arterioles is an important pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-beta1 (TGF-beta1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles.

Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension.

Hypoxia inducible transcription factor (HIF)-1alpha plays an important role in the development of hypoxic pulmonary hypertension, but little is known about HIF-2alpha and HIF-3alpha with respect to transcriptional regulation by hypoxia. To examine the expression patterns of all HIF-alpha subunits (HIF-1alpha, HIF-2alpha and HIF-3alpha) in pulmonary arteries of rats undergoing systemic hypoxia, five groups of healthy male Wistar rats were exposed to normoxia (N) and hypoxia for 3 (H3), 7 (H7), 14 (H14) and 21 (H21) d respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricular hypertrophy index were measured.

[Transforming growth factor beta1 correlates inducible nitric oxide synthase in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension].

Objective: To investigate the dynamic expression of transforming growth factor beta(1)(TGF-beta(1)) and inducible nitric oxide synthase (iNOS) in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension (HPH).

Methods: Forty adult male Wistar rats were randomly divided into five groups: a control group (C group) and groups with hypoxia for 3, 7, 14 and 21 days (H(3), H(7), H(14), H(21) group), eight rats per group. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured.