Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Humans ; Occupational Health ; Refuse Disposal

Objective Pulmonary fibrosis ( PF) is a group of pulmonary interstitial pathological changes caused by various factors, and its pathogenesis is not yet fully elucidated .This article discussed the effect of lycium barbarum polysaccharide ( LBP) on ble-omycin-induced PF in mice and its action mechanisms . Methods The C57/BL6 mice were randomly divided into 6 groups:sham-opera-tion, PF model, dexamethasone ( DM), high-dose LBP, medium-dose LBP, and low-dose LBP.The mice in the sham-operation group were injected into the trachea with isotonic saline and those in the oth-er groups with 5 bleomycin at mg/kg for establishing the PF model . Two days after modeling , the mice in the DM and high-, medium-,and low-dose LBP groups were treated with DM at 5 mg/kg and LBP at 0.8, 0.4, and 0.2 g/kg, while those in the sham-operation and PF model groups with the same volume of isotonic saline , respectively , qd, for 4 consecutive weeks .Then, the pathological chan-ges of the lung tissue were observed and the hydroxyproline ( HYP) content in the lung tissue was detected for all the animals .RT-PCR was used to determine the relative expressions of the PF-related COL1A1 and α-SMA genes. Results Compared with the PF mod-els, the the high-, medium-, and low-dose LBP groups showed significant increased body weight after 4 weeks of medication ([14.29 ±0.38] vs [16.12 ±0.37], [15.58 ±0.25] and [15.07 ±0.21] g, P<0.01), the high-and medium-dose groups ex-hibited remarkably decreased lung indexes ([0.887 ±0.13] vs [0.847 ±0.22] and [0.859 ±0.18]%, P<0.05), and the high-dose group presented markedly reduced alveolitis score (3.40 ±0.23 vs 3.09 ±0.22, P<0.05), PF score (3.57 ±0.27 vs 3.07 ± 0.31, P<0.01) and HYP content ([0.831 ±0.05] vs [0.786 ±0.07] μg/mg wet weight, P<0.05).In comparison with the mod-el group, the DM, high-dose LBP and medium-dose LBP groups showed significantly decreased gene expressions of COL 1A1 (1.53 ± 0.13 vs 1.26 ±0.10 and 0.98 ±0.17, P<0.05) and α-SMA (5.67 ±0.47 vs 4.19 ±0.28 and 2.29 ±0.31, P<0.05). Conclusion LBP can suppress the progression of bleomycin-induced pulmonary fibrosis by inhibiting the gene expressions of COL 1A1 andα-SMA and decreasing the HYP content in the lung tissue .

The contribution of particles to cardiovascular mortality and morbidity has been enlightened by epidemiologic and experimental studies. However, adverse biological effects of the particles with different sizes on cardiovascular cells have not been well recognized. In this study, sub-cultured human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of pure quartz particles (DQ) of three sizes (DQPM1, <1 μm; DQPM3-5, 3-5 μm; DQPM5, 5 μm) and carbon black particles of two sizes (CB0.1, <0.1 μm; CB1, <1 μm) for 24 h. Cytotoxicity was estimated by measuring the activity of lactate dehydrogenase (LDH) and cell viability. Nitric oxide (NO) generation and cytokines (TNF-α and IL-1β) releases were analyzed by using NO assay and enzyme-linked immunoabsorbent assay (ELISA), respectively. It was found that both particles induced adverse biological effects on HUVECs in a dose-dependent manner. The size of particle directly influenced the biological activity. For quartz, the smaller particles induced stronger cytotoxicity and higher levels of cytokine responses than those particles of big size. For carbon black particles, CB0.1 was more capable of inducing adverse responses on HUVECs than CB1 only at lower particle concentrations, in contrast to those at higher concentrations. Meanwhile, our data also revealed that quartz particles performed stronger cell damage and produced higher levels of TNF-α than carbon black particles, even if particles size was similar. In conclusion, particle size as well as particle composition should be both considered in assessing vascular endothelial cells injury and inflammation responses induced by particles.

Boronic Acids ; therapeutic use ; Bortezomib ; Humans ; Male ; Middle Aged ; POEMS Syndrome ; therapy ; Peripheral Blood Stem Cell Transplantation ; Pyrazines ; therapeutic use ; Transplantation, Autologous

Objective To investigate the effects of different combinations of vitamin (Vit) C, Vit E and GSH on the biochemical markers and bone mineral density (BMD) in ovariectomized rats. Methods Seventy female SD rats aged 4 months were divided into two groups, 20 rats with sham operation in control group and 50 rats with bilateral oophorectomy in model group. 3 months later, 10 rats in the model group and 10 rats in the control group were randomly selected and their body weight, uterus weight, BMD of the left femurs and lumbar spines,biomeehanical characteristics of the left femurs, serum levels of Ca2+ , creatinine (Cr), alkaline phosphatase (ALP),superoxide dismutase (SOD) , malondialdehyde (MDA) , GSH-peroxidase (GSH-Px) and serum resisting abilities to OH- were determined. Then the rest rats were divided into five groups: A (sham), B (OVX control), C (Vit C +Vit E), D (GSH) and E (Vit C +Vit E +GSH). Vit C, Vit E and GSH were given 750rng/kg, 250 mg/kg, and 125 mg/kg, respectively daily for 3 months. And then the biochemical markers and BMD were measured. Results 3 months after treatment with antioxidants, BMD of left femurs and lumbars spines was increased, while the level of serum ALP was decreased markedly in B, C and D group as compared with that in B group. The serum level of SOD, GSH-Px and serum resisting ability to OH- were increased in D and E groups and the level of MDA decreased in C and D groups as compared with that in B group. Conclusion Vit C, Vit E and GSH increased BMD, prevented the decrease of SOD and GSH-Px and elevated serum resisting ability to OH-in ovariectomized rats.

Objective To investigate the effects of different combinations of antioxidants VitC, VitE and GSH on the biomechanical and biochemical markers in ovariectomized rats, Methods Seventy female SD rats, aged 4 months, were divided into 2 groups (control and model) randomly. Fifty rats in the model group underwent ovariectomy, while the other 20 rats in the control group had sham operations. Three month slater, 10 rats in the model group and 10 rats in the control group were selected randomly to detect their body weight, uterus weight, BMD of the left femur and lumbar vertebra, biomechanical characteristics of the left femur, levels of serum Ca2 +, Cr, ALP, SOD, MDA and GSH-Px and serumal resistance to OH<'->. Then the rest were divided into 5 groups: A (sham), B (model), C (VitC + VitE), D (GSH), and E (VitC + VitE +GSH). VitC, VitE and GSH were given in 750 mg/kg, 250 mg/kg, and 125 mg/kg every day for 3 months,respectively. And then the biomechanical and biochemical markers were measured. Results Three months after ovariectomy, the body weight of the rats in the model group increased markedly compared with the control group, while BMD of the left femur and lumbar vertebra, biomechanical maximal load and uterus weight decreased. The serum levels of Ca<'2+>, ALP and Cr increased. Three months after antioxidant treatment,the biomechanical maximal load and elastic load of the left femur and the maximal load of the 5th lumbar vertebra, the serum levels of SOD, GSH-Px and the serumal resistance to OH<'-> in groups D and E increased markedly, while the serum level of MDA decreased in groups C and D and the level of serum ALP decreased in all the treatment groups. Conclusion GSH and combination of VitC, VitE and GSH play a positive role in treatment of osteoperesis in ovariectomized rats.

[ABSTRACT]OBJECTIVETo investigate the relationship between upper airway MRI parameters and the severity of patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Then the values of upper airway MRI parameters in waking state were assessed.METHODS The MRI upper airway parameters of 37 OSAHS patients and 18 nonsnoring normal subjects were measured and compared. Then data analysis were carried out to find out significant correlations between the MRI upper airway parameters and the severity of patients (the apnea hypopnea index, AHI; the lowest oxygen saturation, LSaO2; the oxygen desaturation index, ODI) with OSAHS.RESULTSThe correlation between cross-sectional areas and left-right diameter in the narrowest retropalatal region, the thickness of lateral pharyngeal wall, the length of the tongue, the length and thickness of the soft palate and the cross-sectional areas of the soft palate on midsagittal planes and severity of OSAHS were found (P<0.05).CONCLUSIONThe MRI upper airway parameters can be used in evaluating the severity of OSAHS in some ways, locating the obstruction sites and choosing the best treatment planning.

Objective To explore role of 64-slices spiral CT in differetiation of acute chest pains.Methods Thirty six patients with acute chest pains were performed 64-slices spiral CT chest angiography.Two-dimensional and three-dimensional reconstruction was performed in all patients by means of multiplanar reconstruction(MPR)(coronal,sgittal oblique),curved planar reformation(CPR), maximum intensity projection(MIP),and volume rendering(VR).All images were blindly reading by two experienced radiologist.DSA were performed at the same time in 16 cases.Results The coronary artery branches,pulmonary artery and aortic artery in all patients were showed clearly,The acute myocardial infarction were showed in 10 cases,The pulmonary artery embolism in 14 cases,The aortic dissection in 6 cases respectively,The Coronary embolism in One case ,pneumothorax In One case The constrictive pericarditis in 1 case respectively.Normal findings in 4 cases.Conclusion 64-slices spiral CT is a useful and noninvasive examination in acute chest pain.

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.