Mismatch negativity as a potential neurobiological marker of early-stage Alzheimer disease and vascular dementia.

Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits.

Study and Test of a New Bundle-Structure Riser Stress Monitoring Sensor Based on FBG.

To meet the requirements of riser safety monitoring in offshore oil fields, a new Fiber Bragg Grating (FBG)-based bundle-structure riser stress monitoring sensor has been developed. In cooperation with many departments, a 49-day marine test in water depths of 1365 m and 1252 m was completed on the "HYSY-981" ocean oil drilling platform. No welding and pasting were used when the sensor was installed on risers. Therefore, the installation is convenient, reliable and harmless to risers. The continuous, reasonable, time-consistent data obtained indicates that the sensor worked normally under water. In all detailed working conditions, the test results show that the sensor can do well in reflecting stresses and bending moments both in and in magnitude. The measured maximum stress is 132.7 MPa, which is below the allowable stress. In drilling and testing conditions, the average riser stress was 86.6 MPa, which is within the range of the China National Offshore Oil Corporation (CNOOC) mechanical simulation results.

Molecular mechanism of anti-prostate cancer activity of Scutellaria baicalensis extract.

Scutellaria baicalensis is a widely used Chinese herbal medicine historically used in antiinflammatory and anticancer therapy. The goals of the study were to 1) determine its in vitro and in vivo anti-prostate cancer activity, 2) investigate its molecular mechanism directed at cell proliferation control including cyclooxygenase-2(COX-2) prostaglandin E2 (PGE2) and cyclins/cdks pathways, and 3) compare it with those of PC-SPES (PC stands for prostate cancer and spes is Latin for hope), a former herbal mixture for prostate cancer treatment of which S. baicalensis is a major constituent. Two human prostate cancer cell lines (LNCaP, androgen dependent, and PC-3, androgen independent) were assessed for growth inhibition. S. baicalensis exerted dose- and time-dependent increased growth inhibition in both cell lines. However, the PC-3 cells IC50 (50% growth inhibition concentration) were slightly more sensitive than LNCaP cells (IC50=0.15 mg/ml), although the former is androgen independent. S. baicalensis was more effective in inhibition of cell growth compared with PC-SPES (IC50=0.38 mg/ml for PC-3 cells). Significant reduction of PGE2 synthesis in both cells after treatment with S. baicalensis resulted from direct inhibition of COX-2 activity rather than COX-2 protein suppression. S. baicalensis also inhibited prostate-specific antigen production in LNCaP cells. Finally, S. baicalensis suppressed expression of cyclin D1 in LNCaP cells, resulting in a G1 phase arrest, while inhibiting cdk1 expression and kinase activity in PC-3 cells, ultimately leading to a G2/M cell cycle arrest. Animal studies showed a 50% reduction in tumor volume after a 7-wk treatment period. This study demonstrated that S. baicalensis may be a novel anticancer agent for the treatment of prostate cancer.

Novel biodegradable HSAM nanoparticle for drug delivery.

The systemic pharmacological treatment of disease is limited by severe toxicity to normal organs/tissue. Therefore, various delivery vehicles have been designed to carry therapeutic drugs to their target tissues. We designed a novel vehicle formed by the interaction of biotins in a DNA (polymer) with avidins (crosslink), resulting in a porous particle. This self-assembled (HSAM) nanoparticle vehicle has been tested in our laboratory both in vitro and in vivo for its ability to carry doxorubicin, a widely used anticancer drug with a high toxicity to normal organs. Doxorubicin binds to the nanoparticle by intercalating into the DNA strands that are later degraded by nucleases released from cancer cells. Our results showed that 1.1 microg of HSAM DNA can carry 1 microg of doxorubicin, and the doxorubicin-bound HSAM nanoparticle can still be degraded by nucleases (BAL-31 and DNase I). The HSAM nanoparticle carrying doxorubicin can efficiently inhibit cancer cell growth in vitro and in a murine model. Furthermore, this nanoparticle is able to deliver up to 180 ng/mg of doxorubicin to the target tumor tissue, which is 15-fold above the systemic toxicity dose (12 mg/kg). These results suggest that the HSAM nanoparticle is both biocompatible and biodegradable, making it a valuable vehicle for drug delivery in cancer treatment.

Quality evaluation of commercial extracts of Scutellaria baicalensis.

Botanical products have been widely used for various illnesses and general well-being. However, quality control of botanical products is often not performed due to lack of standardization, resulting in inconsistent efficacies and sometimes serious toxicity. The goals of this study were to determine the correlation between chemical composition and biological activities and to establish a method to measure authenticity, chemical consistency, and biological potency of botanical products. A high-performance liquid chromatography method was used to analyze the authenticity and chemical composition of 10 different commercial extracts. The cell viability assay and prostaglandin E2 (PGE2) enzyme immunoassay were used to analyze biological potency and consistency. Our results showed all extracts contained marker components (baicalein and/or baicalin), confirming their authenticity. However, significant product-to-product and batch-to-batch variation of these marker components was observed with 4 products containing no baicalin at all and baicalein concentration ranging from 0 to 52.3 g/mg. The 50% growth inhibition concentration of the extracts ranged from 0.18 to 2.0 mg/ml, more than an 11-fold variation. PGE2 levels varied from 19.5 to 111.1 pg/106 cells, more than a 5.7-fold difference. These results demonstrated significant variation in chemical composition and biological activities of the commercial extracts and that the amount of marker components may not reflect biological activity levels. Therefore, chemical analysis alone is inadequate for quality control, and biological assays must be included for botanical products to ensure chemical authenticity as well as pharmacological/biological potency and consistency.

Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis.

Scutellaria baicalensis is a widely used Chinese herbal medicine that has been used historically in anti-inflammatory and anticancer therapy. The purpose of this study is to verify its anticancer activity on head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E(2) (PGE(2)) and is highly expressed in HNSCC. Two human HNSCC cell lines (SCC-25 and KB) and a nontumorigenic cell line (HaCaT) were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with Scutellaria baicalensis extract. Its effects were compared with those of baicalein (a flavonoid isolated from Scutellaria baicalensis), indomethacin (a nonselective COX inhibitor), and celecoxib (a selective COX-2 inhibitor). Four nude mice with s.c. inoculation of KB cells were tested for its anticancer activity in vivo by oral administration of Scutellaria baicalensis at a dose of 1.5 mg/mouse (75 mg/kg), five times/week for 7 weeks. Scutellaria baicalensis and other agents demonstrated a strong growth inhibition in both tested human HNSCC cell lines. No growth inhibition of HaCaT cells was observed with Scutellaria baicalensis. The IC(50)s were 150 micro g/ml for Scutellaria baicalensis, 25 micro M for celecoxib, and 75 micro M for baicalein and indomethacin. Scutellaria baicalensis, as well as celecoxib and indomethacin, but not baicalein, suppressed proliferation cell nuclear antigen expression and PGE(2) synthesis in both cell types. Scutellaria baicalensis inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. A 66% reduction in tumor mass was observed in the nude mice. Scutellaria baicalensis selectively and effectively inhibits cancer cell growth in vitro and in vivo and can be an effective chemotherapeutic agent for HNSCC. Inhibition of PGE(2) synthesis via suppression of COX-2 expression may be responsible for its anticancer activity. Differences in biological effects of Scutellaria baicalensis compared with baicalein suggest the synergistic effects among components in Scutellaria baicalensis.