Inhibitory effects of lactoferrin on pulmonary inflammatory processes induced by lipopolysaccharide by modulating the TLR4-related pathway.

This study tested the ability of lactoferrin to modulate pulmonary inflammation. To construct in vitro and in vivo inflammatory lung models, cells from the human lung adenocarcinoma cell line (A549) were exposed to lipopolysaccharide (LPS, 1 µg/mL), and mice (CD-1) were intratracheally administered LPS [10 mg/kg of body weight (BW), tracheal lumen injection], respectively. The A549 cells were preincubated with lactoferrin (10 mg/mL), and the mice were intraperitoneally injected with lactoferrin (100 mg/kg of BW), followed by LPS treatment. The concentrations of proinflammatory cytokines (IL-1ß and TNF-α) in culture medium of A549 cells and in bronchoalveolar lavage fluid of the mice were determined using enzyme-linked immunosorbent assays. The toll-like receptor 4-related pathway (TLR4/MyD88/IRAK1/TRAF6/NFκB) was determined at gene and protein expression levels in A549 cells and mouse lung tissue. Results showed that LPS treatment significantly elevated the concentrations of IL-1ß and TNF-α in the A549 cell culture medium and in bronchoalveolar lavage fluid of the mice; it also elevated both the mRNA and protein expressions of TLR4 and the TLR4 downstream factors in A549 cells and mouse lung tissue. Nevertheless, lactoferrin apparently depressed the releases of IL-1ß and TNF-α from A549 cells and lung tissues stimulated by LPS, and significantly suppressed the TLR4 signaling pathway. Lactoferrin also promoted the enhancement of miR-146a expression in A549 cells and mouse lung tissue. Moreover, 100°C heating for 3 min caused total loss of the previously listed bioactivity of lactoferrin. Collectively, we proved that lactoferrin intervened in LPS-induced inflammation in the pulmonary cell model and in the mouse model, through inhibiting the TLR4-related pathway.

LncRNA RUSC1-AS1 promotes the proliferation of hepatocellular carcinoma cells through modulating NOTCH signaling.

The long non-coding RNA (lncRNA) RUSC1-AS1 has been reported to be dysregulated in the progression of many cancers. Also, RUSC1-AS1 had been detected to be highly expressed in laryngeal squamous cell carcinoma and breast cancer cells, suggesting that RUSC1-AS1 may be a biomarker for cancers. However, the biological role and regulatory mechanism of RUSC1-AS1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we found that RUSC1-AS1 was upregulated in HCC tissues and cells, and predicted unfavorable prognosis of HCC patients. The function assays including colony formation, EdU, TUNEL assay revealed that RUSC1-AS1 facilitated HCC cell proliferation and inhibited HCC cell apoptosis. Furthermore, mechanism assays including luciferase reporter assay and RIP assay demonstrated that RUSC1-AS1 could directly bind to hsa-miR-7-5p. Besides, hsa-miR-7-5p targeted and negatively regulated NOTCH3 expression. Moreover, RUSC1-AS1 sponged hsa-miR-7-5p to upregulate NOTCH3 and to trigger the NOTCH signaling pathway. The rescue assays depicted that RUSC1-AS1 regulated HCC cell proliferation and apoptosis through modulating NOTCH signaling. In conclusion, lncRNA RUSC1-AS1 promoted the proliferation and reduced the apoptosis of HCC cells through activation of NOTCH signaling via hsa-miR-7-5p/NOTCH3 axis.

Investigation and comparison of the anti-tumor activities of lactoferrin, α-lactalbumin, and ß-lactoglobulin in A549, HT29, HepG2, and MDA231-LM2 tumor models.

To investigate the anti-tumor activities of lactoferrin, α-lactalbumin, and ß-lactoglobulin, 4 types of human tumor cells (lung tumor cell A549, intestinal epithelial tumor cell HT29, hepatocellular cell HepG2, and breast cancer cell MDA231-LM2) were exposed to 3 proteins, respectively. The effects on cell proliferation, migration, and apoptosis were detected in vitro, and nude mice bearing tumors were administered the 3 proteins in vivo. Results showed that the 3 proteins (20 g/L) inhibited viability and migration, as well as induced apoptosis, in 4 tumor cells to different degrees (compared with the control). In vivo, tumor weights in the HT29 group (0.84 ± 0.22 g vs. control 2.05 ± 0.49 g) and MDA231-LM2 group (1.11 ± 0.25 g vs. control 2.49 ± 0.57 g) were significantly reduced by lactoferrin; tumor weights in the A549 group (1.07 ± 0.19 g vs. control 3.11 ± 0.73 g) and HepG2 group (2.32 ± 0.46 g vs. control 3.50 ± 0.74 g) were significantly reduced by α-lactalbumin. Moreover, the roles of lactoferrin, α-lactalbumin, and ß-lactoglobulin in regulating apoptotic proteins were validated. In summary, lactoferrin, α-lactalbumin, and ß-lactoglobulin were proven to inhibit growth and development of A549, HT29, HepG2, and MDA231-LM2 tumors to different degrees via induction of cell apoptosis.

Long noncoding RNA SNHG15, a potential prognostic biomarker for hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to investigate the expression of lncRNA SNHG15 and its prognostic value in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Expression levels of lncRNA SNHG15 in 152 pairs of HCC tissues and adjacent normal tissues were detected by quantitative real-time PCR. Associations between clinicopathological parameters and lncRNA SNHG15 expression were evaluated using chi-square tests. The overall survival was analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Univariate and multivariate Cox regression analyses were conducted to determine whether lncRNA SNHG15 was an independent predictor of survival. RESULTS: The lncRNA SNHG15 expression was significantly upregulated in tumor tissues compared with that in adjacent non-tumor tissues (p < 0.01). It is also proved that lncRNA SNHG15 expression was associated with histological grade (p = 0.000), TNM stage (p = 0.015), and vein invasion (p = 0.000). In addition, Kaplan-Meier analysis showed that increased LncRNA SNHG15 expression was associated with poor overall survival of patients (p = 0.0011). Moreover, the results of the multivariate analysis showed that high lncRNA SNHG15 expression was a significant independent predictor of poor survival in HCC (p < 0.05). CONCLUSIONS: Our findings suggest that lncRNA SNHG15 may serve as an efficient clinical biomarker and a therapeutic target for HCC patients.

Carotid arterial intima­media thickness and arterial stiffness in pre-eclampsia: analysis with a radiofrequency ultrasound technique.

OBJECTIVE: Whether arterial elasticity is reduced in preeclampsia has been investigated only rarely. This study aimed to characterize in vivo the carotid arterial intima­media thickness (IMT) and mechanical properties in women with pre-eclampsia by employing a radiofrequency ultrasound technique. METHODS: We included 22 late-onset pre-eclamptic pregnant women and 28 normotensive pregnant women who were matched for age (29 ± 6 vs. 27 ± 3, P=0.09) and gestational age (36.0 ± 3.2 vs. 35.8 ± 2.4 weeks, P=0.802). All women were nulliparous with singleton pregnancy. The pre-eclamptic women had a significantly higher arterial pressure than did the normotensive women (P<0.0001). All women underwent right common carotid arterial measurements with an ultrasound machine equipped with automatic Quality IMT (QIMT) and Quality Arterial Stiffness (QAS) capability. At follow-up examination 18 months after parturition, measurements were repeated in 10 of the pre-eclamptic women and 11 of the normotensive women. RESULTS: In pre-eclamptic compared with normotensive pregnancy, carotid arterial IMT (459 ± 95 vs. 351 ± 85 µm, P=0.0001), internal diameter (7.8 ± 0.5 vs. 7.2 ± 0.4 mm, P<0.0001), pulse wave velocity (7.1 ± 1.7 vs. 6.0 ± 1.5 m/s, P=0.007), augmentation index (7.9 ± 9.2 vs. −5.0 ± 5.6%, P<0.0001) and arterial wall tension (55.0 ± 6.5 vs. 38.6 ± 4.9 mmHg/cm, P<0.0001) were significantly greater, and the distensibility coefficient (0.020 ± 0.009 vs. 0.029 ± 0.011 1/kPa, P=0.006) was significantly smaller, remaining so after adjusting for body mass index and carotid arterial pressure. Eighteen months after parturition, carotid arterial internal diameter, pressure and wall tension remained greater in the pre-eclamptic group. CONCLUSION: Carotid arterial remodeling, including changes in arterial internal diameter and wall thickness, and arterial stiffening occur in pre-eclampsia but this may reverse, to some extent, postpartum. QIMT and QAS techniques together could provide a comprehensive assessment of carotid arterial remodeling.

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma.

Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8(+) T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.

Integrated airlift bioreactor system for on-site small wastewater treatment.

An integrated airlift bioreactor system was developed, which mainly consists of a multi-stage loop reactor and a gas-liquid-solid separation baffle and possesses dual functions as bioreactor and settler. This integrated system was used for on-site treatment of industrial glycol wastewater in lab-scale. The strategy of gradually increasing practical wastewater concentration while maintaining the co-substrate glucose wastewater concentration helped to accelerate the microbial acclimation process. Investigation of microbial acclimation, operation parameters evaluation and microbial observation has demonstrated the economical and technical feasibility of this integrated airlift bioreactor system for on-site small industrial wastewater treatment.

Matrix formalism of electromagnetic wave propagation through multiple layers in the near-field region: application to the flat panel display.

We have developed an electromagnetic (EM) wave propagation theory through a single layer and multiple layers in the near-field and far-field regions, and have constructed a matrix formalism in terms of the boundary conditions of the EM waves. From the shielding efficiency (SE) against EM radiation in the near-field region calculated by using the matrix formalism, we propose that the effect of multiple layers yields enhanced shielding capability compared to a single layer with the same total thickness in conducting layers as the multiple layers. We compare the intensities of an EM wave propagating through glass coated with conducting indium tin oxide (ITO) on one side and on both sides, applying it to the electromagnetic interference (EMI) shielding filter in a flat panel display such as a plasma display panel (PDP). From the measured intensities of EMI noise generated by a PDP loaded with ITO coated glass samples, the two-side coated glass shows a lower intensity of EMI noise compared to the one-side coated glass. The result confirms the enhancement of the SE due to the effect of multiple layers, as expected in the matrix formalism of EM wave propagation in the near-field region. In the far-field region, the two-side coated glass with ITO in multiple layers has a higher SE than the one-side coated glass with ITO, when the total thickness of ITO in both cases is the same.

The development of neurobehavioral toxicology in China: the 1994 Hänninen Lecture.

With the rapid growth of industrialization in China, occupational and environmental exposure to chemicals has increased in frequency and in types of chemical exposures. A growing number of Chinese researchers are showing a special interest in exploring the effects of chemicals on the central nervous system. This paper presents a comprehensive review of neurobehavioral toxicology in China. It describes research into the "reference values" of the Neurobehavioral Core Test Battery (NCTB) tests, the development and improvement of the computer-administered Chinese version of the Neurobehavioral Evaluation System (NES-C), and exploration of related biomarkers. On the basis of this research, baseline data for the reference values for six subtests of the NCTB were preliminarily recommended. The upgraded NES-C2 has proven to possess higher stability and validity compared with the previous version, NES-C. Biomarkers derived from the changes in levels of neurotransmitter metabolites might be used as supplementary biomarkers of Pb-induced neurotoxicity.

Determination of serum and urinary aluminum by HPLC with fluorometric detection of Al-lumogallion complex.

We describe a simple and sensitive HPLC method for quantifying aluminum (Al) in biological fluids by measuring the fluorescence of the Al-lumogallion complex (excitation wavelength 500 nm, emission wavelength 575 nm). Serum samples are deproteinized with 0.83 mol/L perchloric acid and centrifuged; the supernates are mixed with lumogallion reagent. Urine samples are pretreated with sodium hydroxide (2 mol/L) and methanol, kept for 1 h at -20 degrees C, and then centrifuged; the precipitate is resuspended in perchloric acid and mixed with lumogallion reagent, as for serum. The maximal fluorescence complex is formed after 1 h at pH 5 +/- 0.5. The HPLC mobile phase consists of (per liter) 100 mL, of 0.2 mol/L potassium hydrogen phthalate, 220 mL of acetonitrile, and distilled deionized water. The flow rate is 1 mL/min, and the injection volume is 5 microliters. The major aluminum species is eluted at 3.5 min, the lowest detection limit being 0.45 pg. We validated the method with samples collected from normal subjects and from workers occupationally exposed to aluminum. Comparing the results with those by traditional atomic absorption spectrometry of urinary aluminum suggests that the proposed method is reliable.

Alterations of monoamine metabolites and neurobehavioral function in lead-exposed workers.

Neurobehavioral and neurochemical effects of occupational lead exposure were investigated by WHO Neurobehavioral Core Test Battery (NCTB) testing and a series of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the exposed group compared with that of the controls (70.55 micrograms/dL vs 3.67 micrograms/dL; and 294.92 micrograms/dL vs 38.32 micrograms/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed workers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is positively correlated with PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.

[Neuropsychological effects of lead exposure].

Neuropsychological effects of lead exposure were studied with WHO recommended Neurobehavioral Core Test Battery (NCTB) and factor analysis in 78 workers occupationally exposed to lead and 76 nonexposed controls with mean blood lead levels of 2.14 mumol/L and 0.20 mumol/L, respectively. Except for the length of employment and average monthly income, there was no significant difference in other aspects of both groups. Lead-exposed workers with blood lead level or more than 2.72 mumol/L showed mild impairment to their motor coordination and memory functions. It also showed a dose-response tendency between blood lead levels and scores of five relevant factors.

Measurements of the thermo-optic coefficient of a barium fluoride single crystal.

The thermo-optic coefficient dn/dT of single-crystal barium fluoride is measured with a precision spectrometer. The values over the visible region in the 30-90 °C and 90-150 °C ranges are -18.8 and -19.7 × 10(-6)/°C, respectively.

Fanning effects in photorefractive crystals.

A model to describe the fanning effect based on the beam-coupling mechanism in photorefractive crystals is presented. The intensity distribution of the fanning beam in a 45 degrees -cut BaTiO(3) crystal is measured experimentally. The results show good quantitative agreement with theory.

[Determination of hydroxygenkwanin and genkwanin in flos Genkwa before and after processing by a TLC-scanner].

Thin-layer chromatography and a dual wavelength TLC-scanner (Shimadzu CS-910) were used for the determination of hydroxygenkwanin and genkwanin in flos Genkwa before and after processing with vinegar. The result shows that the amounts of hydroxygenkwanin and genkwanin in processed products were increased. The amounts of the said two constituents were different in various products.