Tea biochar-immobilized Ralstonia Bcul-1 increases nitrate nitrogen content and reduces the bioavailability of cadmium and chromium in a fertilized vegetable soil.

Pyrolytic biochar (PL-BC, pyrochar) and hydrothermal biochar (HT-BC, hydrochar) derived from branches and leaves of tea plants had different pH, electrical conductivity (EC), total carbon nitrogen content, BET surface area, total pore volume, average pore diameter, and functional groups. HT-BC had a larger specific surface area and more functional groups than PL-BC. Ralstonia Bcul-1 (R-B) was the dominant and functional bacteria in a fertilized vegetable soil supplemented with TBB-immobilized R-B (TBB + R-B). R-B vitality was more closely related to BET surface area, total pore volume, and functional groups of tea-based biochar (TBB: PL-BC and HT-BC). R-B was able to maintain high oxidase activity. R-B and TBB + R-B can increase the activities of urease and peroxidase in vegetable soil playing an essential role in the biotransformation of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N). TBB was able to simultaneously increase the content of NO3--N and NH4+-N, and TBB + R-B also significantly increased NO3--N content but decreased NH4+-N content in a fertilized vegetable soil. These results indicated that R-B promoted nitrification in the soil, i.e. conversion of NH4+-N into NO3--N, by enhancing the activities of urease and peroxidase. R-B had high adsorption capacity for cadmium (Cd) and chromium (Cr) (Cd&Cr: Cd and Cr). Moreover, TBB + R-B was able to convert weak acid extractable and reducible Cd&Cr into a more stable residual fraction and oxidizable Cd&Cr. The overall effect of the treatments was to reduce plant uptake of Cd&Cr by cabbage. TBB + R-B significantly promoted R-B growth, changed inorganic nitrogen speciation, increased NO3--N supply, reduced Cd&Cr bioavailability, and decreased plant tissue Cd&Cr content.

A green initiative for oiled sand cleanup using chitosan/rhamnolipid complex dispersion with pH-stimulus response.

The released oil can affect the vulnerable shoreline environment if the oil spills happen in coastal waters. The stranded oil on shorelines is persistent, posing a long-term influence on the intertidal ecosystem after weathering. Therefore, shoreline cleanup techniques are required to remove the oil from the shoreline environment. In this study, a new shoreline cleanup initiative using chitosan/rhamnolipid (CS/RL) complex dispersion with pH-stimulus response was developed for oiled sand cleanup. The results of factorial and single-factor design revealed that the CS/RL complex dispersion maintained high removal efficiency for oiled sand with different levels of oil content in comparison to using rhamnolipid alone. However, the increase of salinity negatively affected the removal efficiency. The electrostatic screening effect of high ionic strength can hinder the formation of the CS/RL complex, and thus reduce removal efficiency. The pH-responsive characteristic of chitosan allows the easy separation of water and oil in washing effluent. The chitosan polyelectrolytes aggregated and precipitated due to the deprotonation of amino groups by adjusting the pH of the washing effluent to above 8. The microscope image demonstrated that the chitosan aggregates wrapped around the oil droplets and settled to the bottom together, thus achieving oil-water separation. Such pH-stimulus response may help achieve an easy oil-water separation after washing. These findings have important implications for developing the new strategies of oil spill response.

[Effect of acupuncture on pain-emotion related brain regions in patients with cervical spondylosis of cervical type: a fMRI study].

OBJECTIVE: To observe the changes of functional connectivity of brain pain-emotion regulation region in patients with cervical spondylosis of cervical type by functional magnetic resonance imaging (fMRI). METHODS: Thirty-two subjects were selected. Of them, 16 patients with cervical spondylosis of cervical type were divided into an observation group and 16 healthy subjects into a control group. The patients in the observation group were treated with acupuncture at Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and ashi points for 30 min. The rest-state fMRI data was collected before and after acupuncture in the observation group. The subjects in the control group received no treatment, and the rest-state fMRI data was collected once. The visual analogue scale (VAS) score before and after treatment and the pain catastrophizing scale (PCS) score before treatment in the observation group were recorded. The resting-state brain functional imaging characteristics between the observation group and control group before treatment, between the observation group before and after treatment, were compared. Based on the brain functional connectivity of region of interest (ROI) the changes of functional connectivity in insula and ventral tegmental area (VTA) in emotional regulation brain region were observed, and the correlation between functional connectivity changes and VAS、PCS scores in patients of the observation group was analyzed. RESULTS: In the observation group, the VAS score was (1.94±1.12) after the treatment, which was lower than (5.62±1.20) before treatment (P<0.05). The PCS score before treatment was (19.18±8.42) in the observation group. Compared with the control group, the areas with increased functional connectivity with insula in the observation group before acupuncture included bilateral dorsolateral prefrontal lobe and right middle cingulate gyrus, and the areas with increased functional connectivity with VTA included right central posterior gyrus and right insula. In the observation group, the connectivity coefficient of left insula and left dorsolateral prefrontal lobe (r=0.438, P<0.05), the connectivity coefficient of right insula and right dorsolateral prefrontal lobe (r=0.483, P<0.05) were positively associated with the VAS score. In the observation group, the connectivity coefficient between the right insula and the right middle cingulate gyrus (r=-0.560, P<0.05), the connectivity coefficient between the right VTA and the right insula (r=-0.525, P<0.05) were negatively associated with the PCS score. After acupuncture, the areas with decreased functional connectivity with insula included bilateral posterior central gyrus, right anterior central gyrus, middle cingulate gyrus and left corpus callosum, while the bilateral suboccipital gyrus and left cerebellum showed increased functional connectivity with right insula. The areas with decreased functional connectivity with VTA included bilateral dorsomedial prefrontal cortex, left anterior cingulate gyrus, right middle temporal gyrus and left anterior cingulate gyrus. After acupuncture in the observation group, the functional connectivity of left VTA left dorsomedial prefrontal cortex and left anterior cingulate cortex (r=-0.548, P<0.05), the functional connectivity of right VTA-bilateral dorsomedial prefrontal cortex and left anterior cingulate cortex (r=-0.547, P<0.05) were negatively associated with the PCS score. CONCLUSION: Pain involves the formation and expression of "pain-emotion-cognition". Acupuncture can systematically regulate the brain functional connections between cognitive regions such as dorsal prefrontal lobe and anterior cingulate gyrus and emotional regions such as insula and VTA in patients with cervical spondylosis of cervical type, suggesting that acupuncture has a multi-dimensional and comprehensive regulation effect on pain.

Probing the intermolecular interaction mechanisms between humic acid and different substrates with implications for its adsorption and removal in water treatment.

Humic substance is a ubiquitous class of natural organic matter (NOM) in soil and aquatic ecosystems, which severely affects the terrestrial and aquatic environments as well as water-based engineering systems by adsorption on solids (e.g., soil minerals, nanoparticles, membranes) via different interaction mechanisms. Herein, the chemical force microscopy (CFM) technique was employed to quantitatively probe the intermolecular forces of humic acid (HA, a representative humic substance) interacting with self-assembled monolayers (SAMs, i.e., OH-SAMs, CH3-SAMs, NH2-SAMs and COOH-SAMs) in various aqueous environments at the nanoscale. The interaction forces measured during approach could be well fitted by the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory by incorporating the hydrophobic interaction. The average adhesion energy followed the trend as: NH2-SAMs (∼3.11 mJ/m2) > CH3-SAMs (∼2.03 mJ/m2) > OH-SAMs (∼1.38 mJ/m2) > COOH-SAMs (∼0.52 mJ/m2) in 100 mM NaCl at pH 5.8, indicating the significant role of electrostatic attraction in contributing to the HA adhesion, followed by hydrophobic interaction and hydrogen bonding. The adhesion energy was found to be dependent on NaCl concentration, Ca2+ addition and pH. For the interaction between NH2-SAMs and HA, their electrostatic attraction at pH 5.8 turned to repulsion under alkaline condition which led to the sudden drop of adhesion energy. Such results promised the adsorption and release of HA using the recyclable magnetic Fe3O4 nanoparticles coated with (3-aminopropyl)tiethoxysilane (APTES). This work provides quantitative information on the molecular interaction mechanism underlying the adsorption of HA on solids of varying surface chemistry at the nanoscale, with useful implications for developing effective chemical additives to remove HA in water treatment and many other engineering processes.

Optimization of Ultrasound-Assisted Extraction of Monoterpene Glycoside from Oil Peony Seed Cake.

Ultrasound-assisted extraction (UAE) of total monoterpene glycosides extract (TMGE) from oil peony seed cakes was investigated. The extraction yield was optimized using response surface methodology (RSM). The chemical constituents of the monoterpene glycosides extract were isolated by repeated column chromatography, and the contents of the main isolated monoterpene glycosides in the oil peony seed cakes were determined by HPLC. The optimum conditions were as follows: a liquid-to-solid ratio of 27 mL/g, ultrasonic extraction time of 16 min, ultrasonic extraction temperature of 26 °C, and ethanol concentration of 67%. Under these conditions, the extraction yield of TMGE was 10.24%. Twenty monoterpene glycosides were isolated from the oil peony seed cakes, and compounds 11-12, 16 and 20 showed strong inhibitory activities on NO production. TMGE from oil peony seed cakes can also to be used as promising immunosuppressive drug due to its high content of monoterpene glycosides and immune-inhibitory activity. PRACTICAL AAPPLICATION: The peony seed oil was authorized as a new food by the Ministry of Health of the People's Republic of China. Peony seed cake is one of the most important by-products in the preparation of peony seed oil, and accounts for approximately 40% of the total mass of the peony seed. Total monoterpene glycosides are the main active ingredient of oil peony seed cake. This research has optimized the extraction conditions of total monoterpene glycoside from seeds cake of Paeonia ostii, which will provide useful reference information for further studies, and offer related industries with helpful guidance in practice.

Total glucosides of paeony improves the immunomodulatory capacity of MSCs partially via the miR-124/STAT3 pathway in oral lichen planus.

Mesenchymal stem cells (MSCs) have been used clinically and experimentally to relieve severe immune-related diseases due to their immunomodulatory properties, but these are impaired by inflammation. Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease. In the present study, we found MSCs from OLP with higher expression of interleukin (IL)-6, tumour necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß) and IL-10 compared with control. Total glucosides of paeony (TGP) significantly improves the immunomodulatory function of MSCs by inhibiting IL-6 and TNF-α expression and increasing TGF-ß and IL-10 expression. Moreover, TGP can downregulate p-STAT3 expression through upregulation of miR-124. The changes of IL-6, TGF-ß and p-STAT3 were further confirmed by overexpression and knockdown of miR-124 in MSCs. Taken together, the immune-regulating function of MSCs can be improved by TGP via the miR-124/STAT3 pathway.

Novel protein-lipid composite nanoparticles with an inner aqueous compartment as delivery systems of hydrophilic nutraceutical compounds.

Food protein and lipid based nanoparticles have attracted recent interest as a means of delivering nutraceuticals. Nanoparticle encapsulation of nutraceuticals faces challenges to overcome for it to be readily applied in the food industry, such as low encapsulation efficiency for hydrophilic compounds and poor stability once in the gastrointestinal tract. This research introduces a new protein-lipid composite nanoparticle with a three-layered structure (a barley protein layer, α-tocopherol layer and phospholipid layer) and an inner aqueous compartment to load hydrophilic nutraceuticals. This delivery system showed efficient encapsulation of vitamin B12 (69%) and controlled release behavior in simulated gastrointestinal media. An in vitro cell evaluation demonstrated that nanoparticles could internalize into Caco-2 cells via energy-dependent endocytosis and significantly increase the uptake and transport efficiency of vitamin B12 in this model. In vivo, the developed vitamin B12 loaded nanoparticle showed increased serum vitamin B12 levels upon oral administration and reduced the methylmalonic acid level more efficiently than the free form in rats. A 14-day in vivo toxicity study showed no evidence of toxicity in rats implying the safety of the developed nanoparticles in long term use. Overall, the results of this study show the great potential of the developed nanoparticles in increasing the absorption of vitamin B12 upon oral administration.

AME survey-003 A1-part1: in current China, do you regret you joined the medical profession.

BACKGROUND: The medical workforce constitutes the foundation of the provision of health services in all countries. The effectiveness of health systems and the quality of health services are directly related to the performance of health workers. Satisfaction level of the job affects the quality of care for patients. An anonymous on-line survey was conducted with the aim to obtain a better understanding of the current morale of Chinese medical professionals. METHODS: An online cross-sectional questionnaire based survey was conducted during the period of Sep 10-23, 2015, via the platform provided by DXY (www.dxy.cn), which is the largest medical and paramedical related website in China. In addition to demographics of the participants, a particular question was asked to the participants, in current China do you regret you joined the medical profession? This initial report analyzed the relationship between the participants with 'No' or 'Yes' answers to their demographic characteristics. RESULTS: In total 2,356 DXY users completed the survey, including 1,740 males (73.82%) and 617 females (26.18%), with a mean age of 31.96±7.03 yrs. There were more participants from relatively economically developed eastern coast areas. The N/Y (no regret participants vs. regretted participants ratio) ratio for all participants was 1.06 (P=0.181). The N/Y ratio of males and females was 1.04 and 1.11 respectively, and there was no significant difference in this ratio among them. There were 1,549 participants from IIIA hospitals (65.72%, N/Y ratio =1.15, P=0.008), followed by IIIB & IIA hospitals (25.46%, N/Y ratio =0.87, P=0.086), IIB & II C hospitals (3.7%, N/Y ratio =0.83, P=0.394), and lastly 1A & 1B clinics (2.6%, N/Y ratio =1.35, P=0.249). A total of 1,323 participants (56.13%) were trainee doctors with N/Y ratio of 1.19 (P=0.002), followed by lecturer-level attending specialists (27.79%, N/Y ratio =0.81, P=0.009), associate principle doctors (12.43%, N/Y ratio =1.01, P=0.953), and lastly principle doctors (3.73%, N/Y ratio =1.59, P=0.033). Specialties with less stressful workload such as radiology and traditional Chinese medicine have the highest job satisfaction, while doctors in accident and emergency cluster have the least job satisfaction. Medical professionals from Yunnan, Gansu and Shanxi have relatively higher positive response (higher N/Y ratio), despite the fact that these are not the economically advanced regions in China; while Jiangsu, an economically advanced province, had relatively higher negative response (lower N/Y ratio). CONCLUSIONS: The morale of majority medical professional in China mainland is likely to be positive. Job satisfaction is inversely related to work related stress level, but may not related to the absolute income.

Application of molecular imaging technologies in antitumor drug development and therapy.

Molecular imaging enables noninvasive characterization, quantification and visualization of biological and pathological processes in vivo at cellular and molecular level. It plays an important role in drug discovery and development. The skillful use of molecular imaging can provide unique insights into disease processes, which greatly aid in identifications of target. Importantly, molecular imaging is widely applied in the pharmacodynamics study to provide earlier endpoints during the preclinical drug development process, since it can be applied to monitor the effects of treatment in vivo with the use of biomarkers. Herein, we reviewed the application of molecular imaging technologies in antitumor drug development process ranging from identification of targets to evaluation of therapeutic effect.

Cellular uptake behaviour, photothermal therapy performance, and cytotoxicity of gold nanorods with various coatings.

With the development of Au nanorods for a number of biomedical applications, understanding their cellular responses has become increasingly important. In this study, we systematically evaluated the cellular uptake behaviour and cytotoxicity of Au nanorods with various surface coatings, including organic cetyltrimethylammonium bromide (CTAB), poly(sodium 4-styrenesulfonate) (PSS), and poly(ethylene glycol) (PEG), and inorganic mesoporous silica (mSiO2), dense silica (dSiO2), and titanium dioxide (TiO2). The cellular behaviour of Au nanorods was found to be highly dependent on both the surface coating and the cell type. CTAB-, PSS-, and mSiO2-coated Au nanorods exhibit notable cytotoxicity, while PEG-, dSiO2-, and TiO2-coated Au nanorods do not induce cell injury. Optical imaging studies indicated that the cell type plays a preferential role in Au nanorod cellular uptake. Higher cellular uptake of Au nanorods was seen in U-87 MG, PC-3, MDA-MB-231, and RAW 264.7 cells, as opposed to HepG2 and HT-29 cells. In addition, Au nanorod cellular uptake is also highly affected by serum protein binding to the surface coating. mSiO2-, dSiO2-, and TiO2-coated Au nanorods show significantly higher cellular uptake than PSS- and PEG-coated ones, which results in a better photothermal ablation effect for Au nanorods with the inorganic surface coatings. Our study provides valuable insights into the effects of the surface modification on the biocompatibility, cellular uptake, as well as biomedical functions of Au nanorods.

Hepatic sinusoidal obstruction syndrome caused by herbal medicine: CT and MRI features.

OBJECTIVE: To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. MATERIALS AND METHODS: The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. RESULTS: Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). CONCLUSION: Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.

Analysis of the traditional medicine YiGan San by the fragmentation patterns of cadambine indole alkaloids using HPLC coupled with high-resolution MS.

YiGan San (YGS) has long been used in traditional Japanese and Chinese folk medicine and serves as a potent and novel therapeutic agent to treat Alzheimer's disease. In the present study, a rapid and sensitive method based on HPLC coupled with diode-array detection and quadrupole TOF MS (Q-TOF-MS) was designed to reveal the chemical constituents of YGS. Thirty-six compounds were identified and assigned in YGS, including 14 alkaloids, nine γ-lactones, six flavonoids, three triterpenoid saponinares, two small molecular organic acids, and two other types of compounds. In addition, the accurate fragment weight and MS/MS fragmentation reactions of a subtype indole alkaloid in Uncariae ramulus cum uncis were summarized for the first time to realize rapid identification without reference substances. For the first time, 11 major constituents were comprehensively quantified with a HPLC coupled with triple-quadrupole MS method. A three-section switch was used to realize such multicomponent identification. The contents of saikosaponin B2 and isoliquiritin, which produce anti-inflammatory and antidepressant-like effects, were extremely different, up to 700 times, in two sources of YGS. The developed qualitative and quantitative method was proved to be precise, accurate, and reproducible.

Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor.

Cardiovascular risks increase in postmenopausal women. While vitamin D is supplemented for osteoporosis, it is not known whether it protects renal arterial function during estrogen deficiency. Here we measured changes in renovascular reactivity induced by ovariectomy in rats and examined whether calcitriol, the most active form of vitamin D, was able to correct such changes. The impairment of endothelium-dependent relaxation in renal arteries from ovariectomized rats was effectively reversed by long-term calcitriol treatment. It was also corrected by acute exposure to cyclooxygenase-2 (COX-2) inhibitors and a thromboxane-prostanoid receptor antagonist, respectively. Calcitriol normalized the overexpression of COX-2 and thromboxane-prostanoid receptors in intralobal renal artery segments and aortic endothelial cells isolated from ovariectomized rats. In vitro exposure of the arterial segments to calcitriol for 12 h improved relaxation and downregulated thromboxane-prostanoid receptors. The attenuated nitric oxide production in ovariectomized rat aortic endothelial cells was restored following a 12-h treatment with calcitriol, COX-2 inhibition, or thromboxane-prostanoid receptor antagonism. Thus, impaired endothelium-dependent renal artery relaxation in ovariectomized rats is mediated largely through increased activity and expression of COX-2 and the thromboxane-prostanoid receptor. Calcitriol restores endothelial function through downregulating both signaling proteins during estrogen deficiency.

Comparison of the effects of Mylabris and Acanthopanax senticosus on promising cancer marker polyamines in plasma of a Hepatoma-22 mouse model using HPLC-ESI-MS.

A simple and sensitive method for the simultaneous determination of plasma concentrations of five polyamines in normal and Hepatoma-22 mice, and mice treated with Mylabris and Acanthopanax senticosus was developed by HPLC-ESI-MS. Male Kunming mice were divided into nine groups, a control group (inoculation without treatment), a positive group (Cyclophosphamide), treatment groups [Mylabris (4, 8, 16 mg/kg), Acanthopanax senticosus (6, 12, 24 g/kg)] and a normal group (without inoculation). Twenty-four hours after the last administration, plasma samples were collected. The derived polyamines were separated on a C(18) column by a gradient elution using methanol-water with excellent linearity within the range from 2.5 to 1000 ng/mL. Polyamines were confirmed as useful biochemical markers of hepatoma. The differences in anti-cancer therapeutic efficacy between Mylabris and Acanthopanax senticosus might contribute to the variability of polyamine levels in vivo. This HPLC-ESI-MS method was successfully applied to investigate the relationship between polyamines and cancer in mice and might be a useful method to test the activity of potential anti-tumor drugs.

DL-3-n-Butylphthalide, an anti-oxidant agent, prevents neurological deficits and cerebral injury following stroke per functional analysis, magnetic resonance imaging and histological assessment.

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Simultaneous determination of seven bioactive components in Oolong tea Camellia sinensis: quality control by chemical composition and HPLC fingerprints.

A simple and reliable method of high-performance liquid chromatography (HPLC) was developed for the quality control of oolong tea (the dry leaves of Camellia sinensis ): the quality control included the HPLC fingerprint and the quantitative determination of seven bioactive compounds chemicals, namely, (-)-gallocatechin, (-)-epigallocatechin, (-)-epigallocatechin gallate, caffeine, (-)-epicatechin, gallocatechin gallate, and (-)-epicatechin gallate. The developed analyses of the chemicals excelled in quantifying the chemicals in oolong tea. The chemical fingerprint of oolong tea was established using the raw materials of three main production sites in China, that is, Fujian (southern and northern parts), Taiwan, and Guangdong. The fingerprints from different cultivated sources were analyzed by hierarchical cluster analysis, similarity analysis, principal component analysis (PCA), analysis of variance (ANOVA), and discriminant analysis. The results indicated that the combination of chromatographic fingerprint and quantification analysEs could be used for the quality assessment of oolong tea and its derived products.

Quinacrine enhances cisplatin-induced cytotoxicity in four cancer cell lines.

BACKGROUND: Quinacrine has potential as a chemosensitizer when combined with chemotherapy, but its anti-cancer mechanisms remain unclear. The purpose of this study was to explore the capability of quinacrine to enhance the cytotoxic effects of cisplatin and the underlying mechanism involved. METHODS: The potential role of quinacrine in enhancing the effects of cisplatin was investigated in Hela, SCC-VII, SACC-83 and C6 cancer cell lines with different pathologies. The inhibitory effects of quinacrine plus cisplatin on these cell lines were detected using a CCK-8 assay for viability and a TUNEL assay for apoptosis. The molecules involved in apoptotic signal translation, including cIAP-1, Bax, p53 and cleaved caspase-3, were detected by Western blot to investigate the underlying mechanism. RESULTS: The CCK8 assay showed that quinacrine markedly enhanced the cytotoxicity of cisplatin in a dose-dependant manner in the 4 cancer cell lines. The TUNEL assay showed that treating the 4 cell lines for 24 h with cisplatin plus quinacrine significantly increased the percentage of apoptotic cells compared to treatment with single-agent treatment or untreated controls. Western blot analysis showed that quinacrine plus cisplatin significantly down-regulated cIAP-1 and up-regulated Bax and cleaved caspase-3 expression in Hela and SCC-VII cells compared with single-agent treatment. CONCLUSIONS: Quinacrine has the potential to be used as a chemotherapy adjuvant when combined with cisplatin.

Reduced bone perfusion in osteoporosis: likely causes in an ovariectomy rat model.

PURPOSE: To investigate the cause of reduced vertebral perfusion in a rat ovariectomy model. MATERIALS AND METHODS: Experimental protocol was approved by the local Animal Experiment Ethics Committee. Twenty-two Sprague-Dawley rats were studied. Computed tomographic bone densitometry and magnetic resonance perfusion imaging were performed at baseline and 2, 4, and 8 weeks after ovariectomy (n = 11) or sham surgery (n = 11). Perfusion parameters analyzed were maximum enhancement (E(max)) and enhancement slope (E(slope)). After the animals were sacrificed, the aorta and femoral artery were analyzed for vessel reactivity, and the lumbar vertebrae were analyzed for marrow content. RESULTS: In control rats, bone mineral density (BMD), E(max), and E(slope) remained constant. In ovariectomy rats, a comparable reduction in BMD and the perfusion parameters at two weeks post-ovariectomy (BMD, 9.3%; E(max), 11.6%; E(slope), 9%) was seen 2 weeks after ovariectomy, and further reductions were seen 4 weeks (BMD, 17.5%; E(max), 15.6%; E(slope), 33%) and 8 weeks (BMD, 18.8%; E(max), 14.2%; E(slope), 33%) after ovariectomy. Endothelial dysfunction was observed in both the aorta and femoral artery of the ovariectomy group but not of the control group. Increased marrow fat area was seen in the ovariectomy group (52.9% vs 21.6%; P < .01) owing to an increase in fat cell number. Decreased erythropoetic marrow area (32.5% vs 48.6%; P < .05) was also observed in the ovariectomy group. CONCLUSION: Reduced bone perfusion occurs in synchrony with reduced BMD. The most likely causes of reduced bone perfusion are a reduction in the amount of erythropoetic marrow and endothelial dysfunction after ovariectomy. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090608/-/DC1.

Biomedical imaging in the safety evaluation of new drugs.

Toxicology accounts for approximately one-third of attrition in new drug development and is a major concern in the pharmaceutical industry. This paper reviews the role of biomedical imaging in the safety evaluation of new candidate drugs. Ex vivo high-resolution three-dimensional imaging of specimens can provide a quick overview of the specimens. Volumetric measurements of tissue structures and lesions can be made with higher precision and reproducibility than histology approaches. As opposed to histology, in vivo animal imaging permits longitudinal studies of the same animals over an extended period of time, with individual animals serving as their own control. Therefore, the number of animals required for a study can be significantly reduced and the intra-subject variability is minimized. Repeated in vivo imaging allows monitoring of the occurrence and progression, or regression, of various structural and functional abnormalities. Compared with other biological assays, imaging can provide anatomically specific information about tissue abnormality. Imaging offers the opportunity to carry forward the same methodology in animal experiments into human studies and has an important role in clinical trials when other safety biomarkers for early toxicities are not available.

N-nitrosodiethylamine-induced pig liver hepatocellular carcinoma model: radiological and histopathological studies.

Experimental research involving animal models plays a critical role in the development and improvement of minimally invasive therapies for hepatocellular carcinoma (HCC). As a large animal, the pig is commonly used for surgery and interventional radiology research. In this study, liver multicentric HCC with cirrhosis was induced in six China Taihu pigs by intraperitoneal injection of 10 mg/kg of N-nitrosodiethylamine once a week for 3 months, followed by a period of 10-12 months without N-nitrosodiethylamine treatment. All pigs were in generally good health until the end of the study. The tumor nodules appeared hyperattenuating in the arterial phase of a dynamic computed tomography (CT) scan. Digital subtraction angiography (DSA) and CT angiography demonstrated that the tumors derived their blood supply mainly from the hepatic artery system. Lipiodol-CT showed Lipiodol retention in tumor areas. The histology and electron microscopic ultrastructure of the chemically induced liver HCC in this study resembled human HCC with a cirrhosis background. An immunohistochemistry study confirmed that the tumors were of hepatocyte origin. All highly, moderately, and poorly differentiated HCC tumors were identified in this study. Cholangiocarcinoma was not seen in any of the animals. Due to its comparable size to human anatomy, the pig liver HCC model would give a better scope for interventional and surgical manipulations than small animal models.