Quanzhen Yiqi decoction attenuates inflammation in mice with smoking-induced COPD by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome.

OBJECTIVE: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease. METHODS: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1ß/IL-18. RESULTS: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1ß and IL-18. CONCLUSION: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.

Schisandrin A regulates the Nrf2 signaling pathway and inhibits NLRP3 inflammasome activation to interfere with pyroptosis in a mouse model of COPD.

Chronic obstructive pulmonary disease (COPD) is a serious chronic lung disease. Schisandrin A (SchA) is one of the most important active ingredients in Schisandra chinensis and has been used to treat various lung diseases in several countries. Here, we studied the pharmacological effect of SchA on airway inflammation induced by cigarette smoke (CS) and explored the therapeutic mechanism of SchA in COPD model mice. Our results showed that SchA treatment significantly improved the lung function of CS-induced COPD model mice and reduced the recruitment of leukocytes and hypersecretion of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF). H&E staining showed that SchA treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. In addition, we found that SchA treatment can stimulate the expression of heme oxygenase-1 (HO-1) through the nuclear factor-erythroid 2-related factor (Nrf2) pathway, significantly reduce oxidative stress, increase catalase (CAT) and superoxide dismutase (SOD) levels, and suppress the level of malondialdehyde (MDA) in COPD model mice. Moreover, SchA treatment suppressed the generation of the NLRP3/ASC/Caspase1 inflammasome complex to inhibit the inflammatory response caused by IL-1ß and IL-18 and pyroptosis caused by GSDMD. In conclusion, our study shows that SchA treatment can inhibit the production of ROS and the activation of the NLRP3 inflammasome by upregulating Nrf-2, thereby producing anti-inflammatory effects and reducing lung injury in COPD model mice. More importantly, SchA exhibited similar anti-inflammatory effects to dexamethasone in COPD model mice, and we did not observe substantial side effects of SchA treatment. The high safety of SchA makes it a potential candidate drug for the treatment of COPD.

Genomic and transcriptional characterization of early esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly heterogeneous cancer that lacks comprehensive understanding and effective treatment. Although multi-omics study has revealed features and underlying drivers of advanced ESCC, research on molecular characteristics of the early stage ESCC is quite limited. MATERIALS AND METHODS: We presented characteristics of genomics and transcriptomics in 10 matched pairs of tumor and normal tissues of early ESCC patients in the China region. RESULTS: We identified the specific patterns of cancer gene mutations and copy number variations. We also found a dramatic change in the transcriptome, with more than 4,000 genes upregulated in cancer. Among them, more than one-third of HOX family genes were specifically and highly expressed in early ESCC samples of China and validated by RT-qPCR. Gene regulation network analysis indicated that alteration of Hox family genes promoted the proliferation and metabolism remodeling of early ESCC. CONCLUSIONS: We characterized the genomic and transcriptomic landscape of 10 paired normal adjacent and early ESCC tissues in the China region, and provided a new perspective to understand the development of ESCC and insight into potential prevention and diagnostic targets for the management of early ESCC in China.

circTMEM181 upregulates ARHGAP29 to inhibit hepatocellular carcinoma migration and invasion by sponging miR-519a-5p.

AIM: Circular RNAs (circRNAs) are a novel class of noncoding RNAs and are conserved in various species. Although numerous circRNAs have been identified, their role in cancer remains unclear. METHODS: The expression of circTMEM181 in 90 paired human hepatocellular carcinoma (HCC) and adjacent nontumor tissues were detected using quantitative reverse transcription-polymerase chain reaction. Transwell assay was performed for functional analysis of HCC cell migration and invasion. Luciferase reporter assay was used to verify the combination of circTMEM181 and miR-519a-5p. RESULTS: In this study, we identified a novel circRNA, named circTMEM181, was downregulated in HCC tissues. Decreased expression of circTMEM181 was associated with shorter overall survival of patients with HCC. CircTMEM181 overexpression reduced HCC cell migration and invasion abilities, while circTMEM181 knockdown increased cell motility. Mechanically, circTMEM181 could directly bind to miR-519a-5p and subsequently upregulate ARHGAP29 protein expression. CONCLUSION: These data provide the first evidence of clinical significance and function of circTMEM181, and suggest the circTMEM181/miR-519a-5p/ARHGAP29 axis in HCC development.

exoRBase 2.0: an atlas of mRNA, lncRNA and circRNA in extracellular vesicles from human biofluids.

Extracellular vesicles (EVs) are small membranous vesicles that contain an abundant cargo of different RNA species with specialized functions and clinical implications. Here, we introduce an updated online database (http://www.exoRBase.org), exoRBase 2.0, which is a repository of EV long RNAs (termed exLRs) derived from RNA-seq data analyses of diverse human body fluids. In exoRBase 2.0, the number of exLRs has increased to 19 643 messenger RNAs (mRNAs), 15 645 long non-coding RNAs (lncRNAs) and 79 084 circular RNAs (circRNAs) obtained from ∼1000 human blood, urine, cerebrospinal fluid (CSF) and bile samples. Importantly, exoRBase 2.0 not only integrates and compares exLR expression profiles but also visualizes the pathway-level functional changes and the heterogeneity of origins of circulating EVs in the context of different physiological and pathological conditions. Our database provides an attractive platform for the identification of novel exLR signatures from human biofluids that will aid in the discovery of new circulating biomarkers to improve disease diagnosis and therapy.

LncRNA RAD51-AS1/miR-29b/c-3p/NDRG2 crosstalk repressed proliferation, invasion and glycolysis of colorectal cancer.

LncRNAs are recently increasingly emerging as molecules that take its part in human carcinogenesis. A large body of literature has identified the functional roles of lncRNAs in the pathophysiology of CRC. The current study was intended to provide new ideas and perspectives for the functional role of lncRNA RAD51-AS1 in regulating CRC progression. Herein, a survey of RAD51-AS1 expression profile in The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) dataset revealed that RAD51-AS1 was downregulated in COAD specimens. Consistently, RAD51-AS1 expression was observed to be lower in CRC cell lines compared with normal cell line (NCM460). In the meanwhile, both the levels of miR-29b-3p and miR-29c-3p were prominently elevated in CRC cells. Functionally, administration of RAD51-AS1 refrained growth, invasion and migration of CRC cells. Additionally, accumulation of RAD51-AS1 hampered glucose consumption and lactate production, as well as the restraint of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) levels. More important, RAD51-AS1 functioned as a competing endogenous RNA (ceRNA) for sponging miR-29b-3p and miR-29c-3p, leading to enhancement of their common target N-myc downstream-regulated gene 2 (NDRG2). Mechanistically, the delivery of miR-29b/c-3p mimics or ablation of NDRG2 effectively blunted the salutary effects of RAD51-AS1 on CRC cell behaviors. Moreover, augmentation of RAD51-AS1 inhibited the tumorigenesis of CRC cells in vivo. Collectively, these findings provide comprehensive evidence that RAD51-AS1 repressed cell proliferation, migration, invasion and glycolysis process, ultimately contributing to the progression of CRC by repressing the miR-29b/c-3p/NDRG2 signaling axis, insinuating the putative potential of RAD51-AS1/miR-29b/c-3p/NDRG2 interaction network in unraveling CRC pathology and hopefully contributed to the treatment of CRC patients.

miR­204­5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER­2.

Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR­204­5p in gastric cancer. The mRNA expression levels of miR­204­5p in gastric cancer were determined by reverse transcription­quantitative PCR. Cell proliferation was determined using Cell Counting Kit­8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR­204­5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER­2) was predicted using a bioinformatics algorithm and confirmed using a dual­luciferase reporter assay. miR­204­5p levels were downregulated in gastric cancer cells. Overexpression of miR­204­5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR­204­5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR­204­5p, along with increased expression levels of Bax and decreased expression levels of Bcl­2. HER­2 was a direct target of miR­204­5p, and inhibition of HER­2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR­204­5p expression. These results suggested that miR­204­5p could exert its anti­tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER­2, which may be a potential therapeutic target for gastric cancer.

Temperature tuned syntheses of two new d10-based Cd(ii) cluster metal-organic frameworks: luminescence sensing and photocatalytic properties.

The solvothermal reactions of 5,5'-(1,4-phenylenebis(methyleneoxy))diisophthalic acid (H4L) and the N-donor ancillary ligand 3,3',5,5'-tetramethyl-4,4'-bipyrazole (bpz) with cadmium(ii) salts at two different reaction temperatures yielded two new metal-organic frameworks (MOFs), viz., [Cd(H2L)(bpz)] n (1) and [Cd2(H4L)(L)(bpz)2] n (2), which have been characterized by FTIR and single crystal X-ray diffraction. The single crystal X-ray diffraction studies revealed that 1 displays a 3-periodic network with monometallic SBU, while 2 exhibits a 3-periodic network with a 2-fold interpenetration feature. The effects of variation in reaction temperature on the architecture of MOFs 1 and 2 have been discussed. The luminescence investigation indicates that both 1 and 2 displayed good turn-off luminescence sensing against nitroaromatic compounds (NACs), especially m-nitrophenol (MNP), via a decrease in their luminescence intensities with a K sv value of 6.43 × 103 for 1 and 2.03 × 104 for 2 and LOD values of 1.09 and 0.81 ppm for 1 and 2, respectively. The plausible mechanism for the decline in luminescence intensity of the MOFs with NACs has been addressed using theoretical calculations. The photocatalytic properties for both the MOFs demonstrated that they display efficient photocatalytic performances to degrade methyl violet (MV) under UV irradiation. The plausible mechanism through which these MOFs exhibited photocatalytic properties has been suggested using band gap calculations.

Gene Expression and Correlation of Pten and Fabp4 in Liver, Muscle, and Adipose Tissues of Type 2 Diabetes Rats.

BACKGROUND: The aim of this work was to study the Fabp4 and Pten gene expression and correlation in the liver, muscle, and adipose tissues of type 2 diabetes mellitus (T2DM) rats. MATERIAL AND METHODS: Male Wistar rats (8 weeks old) were randomly divided into 2 groups (n=12/group): a control group fed a normal diet for 8 weeks and an experimental group fed a high-fat, high-sugar diet for 8 weeks and that received 25 mg/kg streptozotocin by intraperitoneal injection to induce T2DM. The random blood glucose, fasting blood glucose, and fasting insulin levels were measured. The expression of Pten and Fabp4 in the liver, muscle, and epididymal adipose tissues was estimated by real-time quantitative PCR. Pearson correlation coefficient analysis was used to investigate the expression correlation between Pten and Fabp4 in T2DM rats. RESULTS: The gene expressions of Pten and Fabp4 in the liver, muscle, and adipose tissues of T2DM rats were all significantly higher than those in the control group (P<0.05). Pten was highly expressed in the muscles and Fabp4 was highly expressed in muscle and adipose tissues. Furthermore, expressions of Fabp4 and Pten in the muscle and adipose tissues of T2DM rats were positively correlated (P<0.05), but not in the liver. CONCLUSIONS: The increased expression of PTEN and FABP4 in the adipose and muscles of T2DM rats may play an important role in the insulin resistance of T2DM. However, the mechanism by which these 2 genes function in T2DM needs further study.

Regenerating gene 1B silencing inhibits colon cancer cell HCT116 proliferation and invasion.

BACKGROUND: The human regenerating gene 1B (REG1B) is found to be frequently up-regulated in many types of human tumors. It is unclear whether REG1B expression may have therapeutic value in colorectal carcinoma. Additionally, how REG1B is associated with the clinical features of colorectal carcinoma is not known. To investigate the relationship between REG1B and colorectal cancer, we analyzed REG1B expression in clinical specimens and cell lines and the effect of down-regulation of REG1B by short hairpin RNA (shRNA) in HCT116 cells. METHODS: Paraffin-embedded specimens from 30 pairs of colorectal cancer tissues and adjacent colon tissues were used to investigate the expression of REG1B by immunohistochemistry. We also examined whether REG1B itself may be related to cell proliferation, cell cycle arrest, apoptosis, migration and invasion in colon cancer HCT116 cells. RESULTS: Our results showed that REG1B was highly expressed in colorectal carcinoma and was significantly associated with cell differentiation status. The results also illustrated that REG1B silencing with shRNA inhibited cell proliferation, migration and invasion but did not induce apoptosis. Furthermore, down-regulation of REG1B induces G1-phase cell cycle arrest in colon cancer cells. CONCLUSIONS: Knockdown of REG1B can inhibit cell proliferation, migration and invasion. It may act by a mechanism regulating cell cycle progression. Thus, REG1B may be a novel candidate therapeutic target for colorectal cancer.

Increased plasma levels of FABP4 and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus.

BACKGROUND: The aim of this study was to investigate the relationship between plasma fatty acid binding protein 4 (FABP4), phosphatase and tensin homolog (PTEN), and insulin resistance in patients with gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Plasma FABP4 and PTEN were determined by ELISA in GDM patients (GDM group, n=30) and in euglycemic pregnant women (control group, n=30). The clinical features, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were compared between the 2 groups. The influence of risk factors on insulin resistance, including BMI, lipid profiles, FABP4, and PTEN, were further investigated by multiple-factor stepwise regression analysis. RESULTS: Higher levels of BMI, ΔBMI, triglyceride (TG), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting insulin, HOMA-IR, FABP4, PTEN, and lower level of high-density lipoprotein cholesterol (HDL-C) were found in the GDM patients than in the controls (all P<0.005). The plasma FABP4 was 1.47±0.25 vs. 0.20±0.07 ng/ml in the GDM and control group, respectively (P<0.0001). Plasma PTEN was 6.46±1.57 vs. 4.72±0.82 ng/ml in the GDM and control group, respectively (P<0.0001). There was a positive relation between plasma FABP4 and PTEN when all blood samples, including GDM and control groups, were analyzed (P<0.05). The multiple-factor regression analysis revealed that plasma FABP4, TG, and PTEN were independent risk factors for increased insulin resistance. CONCLUSIONS: GDM patients have more severe insulin resistance compared to euglycemic pregnant women. Higher levels of plasma FABP4 and PTEN are associated with increased insulin resistance and may participate in the pathogenesis of insulin resistance during gestation.

[Involvement of heme oxygenase in PM2.5-toxicity in human umbilical vein endothelial cells].

OBJECTIVE: To investigate the involvement of heme oxygenase (HO-1) in PM2.5 induced toxic responses in human umbilical vein endothelial cells (HUVECs). METHODS: The experiment groups are as follows: (1) control group; (2) PM2.5 groups: the cells were cultured with various concentrations of PM2.5 (200, 400, 800 µg/ml) for 24 h and 400 µg/ml was chosen for the main study; (3) PM2.5+Trion group: the cells were pre-treated by 10 µmol/L Trion [a scavenger of reactive oxygen species(ROS)] for 1 h before PM2.5 (400 µg/ml) treatment for 24 h; (4) PM2.5+ZnPP group: the cells were pretreated by HO-1 inhibitor ZnPP (10 µmol/L) for 1 h before treatment with PM2.5 (400 µg/ml) for 24 h. MTT assay was used to detect cell viability. Reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay were used to determine the mRNA and protein expressions of HO-1. Fluorescence labeling probe method was used to measure intracellular ROS level and flow cytometry was used for cell apoptosis. Colorimetric assay was used to detect intracellular caspase-3 activity. RESULTS: Compared with control, PM2.5 significantly decreased cell viability, increased intracellular ROS, cell apoptosis and caspase-3 activity (all P < 0.05), these effects were significantly attenuated in PM2.5+Tiron group while enhanced in PM2.5+ZnPP group (all P < 0.05 vs. PM2.5 group). PM2.5 upregulated HO-1 mRNA and protein expressions in HUVECs which was downregulated in both PM2.5+Tiron group and PM2.5+ZnPP group. CONCLUSION: PM2.5 could induce oxidative injury through increasing ROS production via modulating HO-1 mRNA and protein expressions, the injury could be aggravated with inhibition of the activity of HO-1 suggesting a potential protective role of HO-1 against PM2.5 induced oxidative stress in HUVECs.

[Study on the effect of extracts from the leaves of Phyllanthus emblica on immune function of mice].

OBJECTIVE: To explore the effect of extracts from the leaves of Phyllanthus emblica (PLFs) on the immune function of mice. METHODS: 70 Kunming mice were choosed to conduct the acute toxicity test of PLFs. The mice were randomly divided into four groups: PLFs high-dosage group, mid-dosage group, low-dosage group and control group. The high,mid,low-dosage groups were treated with PLFs 1.982, 0.991 and 0.496 g/kg respectively per day. The same volume of double distilled water was given to the control group. All by intragastric administration for 7 d. The animals were killed and indexes of thymus and spleen were calculated. The expurgation index K and phagocyte index a were detected after the mice being injected with a dilute India ink through caudal vein. In addition, prepared spleen cells conventionally,the activity of Natural Killer cells was measured and the proliferation of T and B cells were detected. The effect of the extracts on serum hemolysin was detected after the SRBC was injected into the enterocoelia. RESULTS: The LD50 of PLFs was 9. 911 g/kg. Compared with the control group, the indexes of thymus and spleen in the treatment groups had no markedly difference (P > 0.05). The high- and mid-dosage groups could obviously improve the expurgation index K (P < 0.05), phagocyte index alpha (P < 0.05) and NK cell activity (P < 0.05). CONCLUSION: The extracts from Phyllanthus emblica leaves can promote nonspecific immunity immune function in mice.

Ginsenoside Rg1 reduces toxicity of PM(2.5) on human umbilical vein endothelial cells by upregulating intracellular antioxidative state.

Ambient airborne particulate matter (PM) is an important environmental pollutant responsible for many human diseases. Oxidative stress is suggested to be involved in PM-induced cell injury. The present study is designed to study unsalutary effects of the organic extracts of PM with an aerodynamic diameter of less than 2.5µm (PM(2.5)) and protective effect of Ginsenoside Rg1 (Rg1) against PM(2.5) on human umbilical vein endothelial cells (HUVECs) in vitro. Cytotoxic effects of the organic extract PM(2.5) on HUVECs were measured by means of HUVEC cell viability and the generation of intracellular reactive oxygen species (ROS). Expression of heme oxygenase-1(HO-1) and Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Nrf2 cytoplasm-nucleus location were assayed. The present results showed that PM(2.5) (50-800µg/ml) decreased HUVEC viability and increased intracellular generation of ROS and malondialdehyde (MDA) in a concentration dependent manner, but increased HO-1 expression without concentration dependence. Rg1 (10 and 40µg/ml) diminished PM(2.5)-induced HUVEC viability, decrease ROS and MDA generation, increased HO-1 and Nrf2 expression and promoted Nrf2 translocation to nucleus in a concentration dependent manner. These results suggested that organic extracts of PM(2.5) increase oxidative stress and decrease cell viability; Rg1 antagonize PM(2.5)-induced excess oxidative stress; HO-1 expression increase and Nrf2 translocation to nucleus may be involved in the effects of both PM(2.5) and Rg1 on HUVECs.

A focused sulfated glycoconjugate Ugi library for probing heparan sulfate-binding angiogenic growth factors.

A library of small molecule heparan sulfate (HS) mimetics was synthesized by employing the Ugi four-component condensation of d-mannopyranoside-derived isocyanides with formaldehyde as the carbonyl component and a selection of carboxylic acids and amines, followed by sulfonation. The library was used to probe the subtle differences surrounding the ionic binding sites of three HS-binding angiogenic growth factors (FGF-1, FGF-2 and VEGF). Each compound features 3 or 4 sulfo groups which serve to anchor the ligand to the HS-binding site of the protein, with a diverse array of functionality in place extending from C-1 or C-6 to probe for adjacent favorable binding interactions. Selectivity of binding to these proteins was clearly observed and supported by molecular docking calculations.

Synthesis of a heparan sulfate mimetic library targeting FGF and VEGF via click chemistry on a monosaccharide template.

A disulfated methyl 6-azido-6-deoxy-α-D-mannopyranoside template was used as a core structure for binding to the angiogenic growth factors FGF-1, FGF-2, and VEGF. The core structure was diversified in a rapid, parallel manner by employing the Cu(I)-catalyzed Huisgen azide-alkyne cycloaddition ("click") reaction. The diversity was further extended by incorporating a Swern oxidation-Wittig reaction sequence on a click adduct of propargyl alcohol. Thus, the sulfated core was linked by various spacers to selected hydrophobic or polar motifs, which were designed to probe the protein surface surrounding the cationic heparan sulfate binding sites of the growth factors in order to improve affinity and selectivity. The affinities of the compounds for the growth factors were measured by surface plasmon resonance solution affinity assays. A lead compound was identified with micromolar binding affinity toward both FGF-1 and VEGF (K(d)=84 and 49 µM, respectively) and good selectivity over FGF-2 (29- and 51-fold, respectively).

[Effect of ginsenoside on fine particulate matter induced oxidative injury in human endothelial cells].

OBJECTIVE: To explore the mechanism of fine particulate matter (PM(2.5)) induced endothelial injury and the efficacy and mechanism of ginsenoside Rg1 on the inhibition of endothelium injuries in human endothelial cells exposure to PM(2.5). METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with various concentrations PM(2.5) (0.1, 0.2, 0.4, 0.8 mg/ml) and PM(2.5) at concentration 0.8 mg/ml induced significant endothelial injury and was chosen for the main study in the presence or absence of Rg1 (0.04 mg/ml). After 24 h treatment, cell growth A value was detected through MTT, intracellular reactive oxygen species (ROS) level through fluorescence labeling probe method and HO-1, Nrf2 mRNA expression was detected by RT-PCR. RESULTS: The cell A value was significantly lower while the ROS fluorescence gray value and the average optical density ratio of HO-1 were significantly higher in PM(2.5) group than in the control group (all P < 0.05). The average optical density ratio of Nrf2 was similar between PM(2.5) group and control group (P > 0.05). The A value and the average optical density ratio of HO-1 were significantly higher while the ROS fluorescence gray value was significantly lower in co-treated PM(2.5) (0.8 mg/ml) + Rg1 (0.04 mg/ml) group than in the PM(2.5) (0.8 mg/ml) group (all P < 0.05). CONCLUSION: PM(2.5) could induce human endothelial cells injury by increasing oxidative stress which could be attenuated by ginsenoside Rg1.

Design, synthesis, FGF-1 binding, and molecular modeling studies of conformationally flexible heparin mimetic disaccharides.

Disaccharide mimetics of a heparin sequence that binds to fibroblast growth factors were prepared by coupling a D-galactose donor with a methyl beta-D-gluco- or xylopyranoside acceptor. When fully sulfated, the glucose or xylose moieties exist in solution in equilibrium between the (4)C1 and (1)C4 conformers, as confirmed by 1H NMR spectroscopy, thus mimicking the conformationally flexible L-iduronic acid found in heparin. Docking calculations showed that the predicted locations of disaccharide sulfo groups in the binding site of FGF-1 are consistent with the positions observed for co-crystallized heparin-derived oligosaccharides. Predicted binding affinities are in accord with experimental Kd values obtained from binding assays and are similar to the predicted values for a model heparin disaccharide.

PI-88 and novel heparan sulfate mimetics inhibit angiogenesis.

The heparan sulfate (HS) mimetic PI-88 is a promising inhibitor of tumor growth and metastasis expected to commence phase III clinical evaluation in 2007 as an adjuvant therapy for postresection hepatocellular carcinoma. Its anticancer properties are attributed to inhibition of angiogenesis via antagonism of the interactions of angiogenic growth factors and their receptors with HS. It is also a potent inhibitor of heparanase, an enzyme that plays a key role in both metastasis and angiogenesis. A series of PI-88 analogs have been prepared with enhanced chemical and biological properties. The new compounds consist of single, defined oligosaccharides with specific modifications designed to improve their pharmacokinetic properties. These analogs all inhibit heparanase and bind to the angiogenic fibroblast growth factor 1 (FGF-1), FGF-2, and vascular endothelial growth factor with similar affinity to PI-88. However, compared with PI-88, some of the newly designed compounds are more potent inhibitors of growth factor-induced endothelial cell proliferation and of endothelial tube formation on Matrigel. Representative compounds were also tested for antiangiogenic activity in vivo and were found to reduce significantly blood vessel formation. Moreover, the pharmacokinetic profile of several analogs was also improved, as evidenced primarily by lower clearance in comparison with PI-88. The current data support the development of HS mimetics as potent antiangiogenic anticancer agents.

Application of potassium titanyl phosphate (KTP) laser delivered via bronchofiberscope in the treatment of endobronchial tuberculosis.

To explore the application of potassium titanyl phosphate (KTP) laser delivered via bronchofiberscope in the treatment of endobronchial tuberculosis. 36 patients with a diagnosis of endobronchial tuberculosis, with age ranging from 15 to 40 y were treated with KTP laser between Dec. 2002 and July 2004 (designated as treatment group). The other 36 patients diagnosed as having endobronchial tuberculosis (aged 18 to 42 y, with a mean age of 33. 5 y) without having received KTP laser treatment were included in a control group. Our results showed that the effective rates, in terms of recovery of bronchial lumen and cleanup of caseous necrotic mass were significantly higher in the treatment group 8 weeks after the treatment (P<0.01), and the healing rates of atelectasis and obstructive infection were also significantly higher in the treatment group (P<0.05 and P<0.01), but the incidence of complication after 8 weeks was no significant difference (P >0.05). No significant changes were found in SaO2 and HR before, during and after the operation in the treatment group (P>0.05). It is concluded that KTP laser is an effective therapy for endobronchial tuberculosis.