Proteomic approach to study the cytotoxicity of dioscin (saponin)

Dioscin, extracted from the root of Polygonatum zanlanscianense pamp, exhibits cytotoxicity towards human myeloblast leukemia HL-60 cells. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria are the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by dioscin treatment. Changes in proteome other than mitochondrial related proteins implicate that other mechanisms were also involved in dioscin-induced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alterations of phosphatases in cell signaling, and deregulation of oxidative stress and cell proliferation. Current study of protein alterations in dioscin-treated HL-60 cells suggested that dioscin exerts cytotoxicity through multiple apoptosis-inducing pathways. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Survival prediction in high-grade gliomas using CT perfusion imaging.

Patients with high-grade gliomas usually have heterogeneous response to surgery and chemoirradiation. The objectives of this study were (1) to evaluate serial changes in tumor volume and perfusion imaging parameters and (2) to determine the value of these data in predicting overall survival (OS). Twenty-nine patients with World Health Organization grades III and IV gliomas underwent magnetic resonance (MR) and computed tomography (CT) perfusion examinations before surgery, and 1, 3, 6, 9, and 12 months after radiotherapy. Serial measurements of tumor volumes and perfusion parameters were evaluated by receiver operating characteristic analysis, Cox proportional hazards regression, and Kaplan-Meier survival analysis to determine their values in predicting OS. Higher trends in blood flow (BF), blood volume (BV), and permeability-surface area product in the contrast-enhancing lesions (CEL) and the non-enhancing lesions (NEL) were found in patients with OS \u3c 18 months compared to those with OS ≥ 18 months, and these values were significant at selected time points (P \u3c 0.05). Only CT perfusion parameters yielded sensitivities and specificities of ≥70 % in predicting 18 and 24 months OS. Pre-surgery BF in the NEL and BV in the CEL and NEL 3 months after radiotherapy had sensitivities and specificities \u3e80 % in predicting 24 months OS in patients with grade IV gliomas. Our study indicated that CT perfusion parameters were predictive of survival and could be useful in assessing early response and in selecting adjuvant treatment to prolong survival if verified in a larger cohort of patients

Studies on Bioflocculant Production by Arthrobacter sp. Raats, a Freshwater Bacteria Isolated from Tyume River, South Africa

A bioflocculant-producing bacteria was isolated from Tyume River in the Eastern Cape Province, South Africa and identified by 16S rRNA gene nucleotide sequence to have 91% similarity to Arthrobacter sp. 5J12A, and the nucleotide sequence was deposited in GenBank as Arthrobacter sp. Raats (accession number HQ875723). The bacteria produced an extracellular bioflocculant when grown aerobically in a production medium containing glucose as sole carbon source and had an initial pH of 7.0. Influences of carbon, nitrogen and metal ions sources, as well as initial pH on flocculating activity were investigated. The bacteria optimally produced the bioflocullant when lactose and urea were used as sole sources of carbon and nitrogen respectively with flocculating activities of 75.4% and 83.4% respectively. Also, the bacteria produced the bioflocculant optimally when initial pH of the medium was 7.0 (flocculating activity 84%), and when Mg2+ was used as cation (flocculating activity 77%). Composition analyses indicated the bioflocculant to be principally a glycoprotein made up of about 56% protein and 25% total carbohydrate

Assessment of Bioflocculant Production by Bacillus sp. Gilbert, a Marine Bacterium Isolated from the Bottom Sediment of Algoa Bay

The bioflocculant-producing potentials of a marine bacteria isolated from the bottom sediment of Algoa Bay was investigated using standard methods. The 16S rDNA sequence analysis revealed 98% similarity to that of Bacillus sp. HXG-C1 and the nucleotide sequence was deposited in GenBank as Bacillus sp. Gilbert with accession number HQ537128. Bioflocculant was optimally produced when sucrose (72% flocculating activity) and ammonium chloride (91% flocculating activity) were used as sole sources of carbon and nitrogen, respectively; an initial pH 6.2 of the production medium; and Mg2+ as cation. Chemical analysis of the purified bioflocculant revealed the compound to be a polysaccharide

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice

The Effectiveness of Pay-It-Forward in Addressing HPV Vaccine Delay and Increasing Uptake Among 15–18-Year-Old Adolescent Girls Compared to User-Paid Vaccination: A Study Protocol for a Two-Arm Randomized Controlled Trial in China

Background Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9–18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15–18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China. Methods This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series. Discussion This study will investigate an innovative pay-it-forward strategy’s effectiveness and economic costs to improve HPV vaccination among 15–18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee

Towards Intelligent Crowd Behavior Understanding through the STFD Descriptor Exploration

Realizing the automated and online detection of crowd anomalies from surveillance CCTVs is a research-intensive and application-demanding task. This research proposes a novel technique for detecting crowd abnormalities through analyzing the spatial and temporal features of input video signals. This integrated solution defines an image descriptor (named spatio-temporal feature descriptor - STFD) that reflects the global motion information of crowds over time. A CNN has then been adopted to classify dominant or large-scale crowd abnormal behaviors. The work reported has focused on: 1) detecting moving objects in online (or near real-time) manner through spatio-temporal segmentations of crowds that is defined by the similarity of group trajectory structures in temporal space and the foreground blocks based on Gaussian Mixture Model (GMM) in spatial space; 2) dividing multiple clustered groups based on the spectral clustering method by considering image pixels from spatio-temporal segmentation regions as dynamic particles; 3) generating the STFD descriptor instances by calculating the attributes (i.e., collectiveness, stability, conflict and crowd density) of particles in the corresponding groups; 4) inputting generated STFD descriptor instances into the devised convolutional neural network (CNN) to detect suspicious crowd behaviors. The test and evaluation of the devised models and techniques have selected the PETS database as the primary experimental data sets. Results against benchmarking models and systems have shown promising advancements of this novel approach in terms of accuracy and efficiency for detecting crowd anomalies

Towards Intelligent Crowd Behavior Understanding through the STFD Descriptor Exploration

Realizing the automated and online detection of crowd anomalies from surveillance CCTVs is a research-intensive and application-demanding task. This research proposes a novel technique for detecting crowd abnormalities through analyzing the spatial and temporal features of input video signals. This integrated solution defines an image descriptor (named spatio-temporal feature descriptor - STFD) that reflects the global motion information of crowds over time. A CNN has then been adopted to classify dominant or large-scale crowd abnormal behaviors. The work reported has focused on: 1) detecting moving objects in online (or near real-time) manner through spatio-temporal segmentations of crowds that is defined by the similarity of group trajectory structures in temporal space and the foreground blocks based on Gaussian Mixture Model (GMM) in spatial space; 2) dividing multiple clustered groups based on the spectral clustering method by considering image pixels from spatio-temporal segmentation regions as dynamic particles; 3) generating the STFD descriptor instances by calculating the attributes (i.e., collectiveness, stability, conflict and crowd density) of particles in the corresponding groups; 4) inputting generated STFD descriptor instances into the devised convolutional neural network (CNN) to detect suspicious crowd behaviors. The test and evaluation of the devised models and techniques have selected the PETS database as the primary experimental data sets. Results against benchmarking models and systems have shown promising advancements of this novel approach in terms of accuracy and efficiency for detecting crowd anomalies

Impact of Visceral Adiposity Measured by Abdominal Computed Tomography on Pulmonary Function

Although an inverse relationship between abdominal adiposity and pulmonary function has been suggested, direct measurement of abdominal adipose tissue has rarely been attempted. Our object is to determine the impact of abdominal adiposity on pulmonary function by directly measuring abdominal adipose tissue with abdominal computed tomography (CT). In this cross-sectional study, we included never-smokers between the ages of 18 and 85 yr, who had undergone spirometry and abdominal adipose tissue analysis with CT scans during November 1, 2005 to October 31, 2009 as part of the comprehensive health examination. Among a total of 3,469 participants, 890 (25.7%) were male. The mean body mass index and waist circumference among males and females were 24.6 kg/m2 and 87.8 cm and 23.0 kg/m2 and 83.0 cm, respectively. Although total adipose tissue (TAT) of the abdomen in males (269.1 cm2) was similar to that in females (273.6 cm2), the ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) was different; 0.99 in males and 0.50 in females. In males, TAT, SAT, and VAT were inversely associated with the absolute value of forced vital capacity (FVC), and TAT and VAT were inversely associated with forced expiratory volume in one second (FEV1). However, in females, TAT and VAT, but not SAT, were inversely associated with absolute FVC and FEV1 values. In conclusion, the amount of abdominal adipose tissue directly measured using CT is inversely associated with lung function

Antiproliferative and Proapoptotic Activities of Methanolic Extracts from Ligustrum vulgare L. as an Individual Treatment and in Combination with Palladium Complex

The aim of this study is to examine the growth inhibitory effects of methanolic leaf and fruit extracts of L. vulgare on HCT-116 cells over different time periods and their synergistic effect with a Pd(apox) complex. The antiproliferative activity of plant extracts alone or in combination with the Pd(apox) complex was determined using MTT cell viability assay, where the IC50 value was used as a parameter of cytotoxicity. Results show that antiproliferative effects of L. vulgare extracts increase with extension of exposure time, with decreasing IC50 values, except for 72 h where the IC50 values for methanolic leaf extract were lower than for the fruit extract. The Pd(apox) complex alone had a weak antiproliferative effect, but combination with L. vulgare extracts caused stronger effects with lower IC50 values than with L. vulgare extracts alone. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. Treatments with plant extracts caused typical apoptotic morphological changes in HCT-116 cells and co-treatments with Pd(apox) complex caused higher levels of apoptotic cells than treatment with plant extracts alone. The results indicate that L. vulgare is a considerable source of natural bioactive substances with antiproliferative activity on HCT-116 cells and which have a substantial synergistic effect with the Pd(apox) complex