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Thyroglobulin (Tg), the major thyroidal protein, plays important roles in thyroid hormone biosynthesis and in autoimmune thyroid diseases (AITD). Tg also serves as a pre- and postoperative biomarker of differentiated thyroid cancer (DTC). The endogenous β-galactoside binding lectin galectin-3 (Gal-3), secreted by transformed thyroid cells, has been shown to be another useful biomarker of DTC. Tg contains covalently linked complex-type glycans that can serve as binding epitopes of Gal-3. The objective of the study is to investigate the interaction between Tg and Gal-3 and discuss its potential consequences.Binding interaction between Tg and Gal-3 was first studied by hemagglutination inhibition assays. Subsequently, a detailed analysis of binding thermodynamics was carried out by isothermal titration calorimetry. Quantitative precipitation was performed to study the complex formation between Tg and Gal-3 and to determine the binding stoichiometry. The concentration-dependent rate and amount of complex formation between Tg and Gal-3 was examined spectrophotometrically. A similar approach was taken to study the effect of free Tg and Gal-3 on preformed Tg-Gal-3 complex.Quantitative biochemical and biophysical data show that these two biomarkers produced by thyroid cancer cells interact with each other with submicromolar affinity and form an insoluble complex at their stoichiometric concentration. One Tg molecule could bind up to 14 molecules of Gal-3. Such complex formation mutually sequestered both Tg and Gal-3, decreasing the concentration of their freely available forms. Formation of the Tg-Gal-3 complex was reversible as the preformed complex was dissolved by free Tg as well as free Gal-3. While free Tg rapidly dissolved preformed Tg-Gal-3 complex in a concentration-dependent manner, Gal-3 was found to be much less efficient and slowly dissolved only a fraction of the preformed complex at a relatively higher Gal-3 concentration.Complex formation between Tg and Gal-3 through high affinity binding and the sensitivity of the complex to free Tg and Gal-3 can potentially influence their biological functions. Interactions between Tg and Gal-3 might also interfere with their clinical detection, the same way Tg autoantibody (TgAb) is reported to interfere with Tg assays. The data support a model of Gal-3-mediated homeostatic process of Tg.

Bipolar disorder (BD) is associated with alterations of cytokines in the immune system. The aim of this study was to assess the serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state patients of BD. The correlations between the serum cytokines levels with the demographic characteristics and the psychiatric symptoms were also assessed. We measured serum TNF-α, IL-6 and IL-18 levels using an enzyme-linked immunosorbent assay (ELISA) from 59 BD patients (37 in manic state, 12 in depressive state, 10 in mixed state) and 80 healthy control subjects. The psychotic symptoms of BD were assessed using the Hamilton Depression Scale (HAMD) and the Young Mania Rating Scale (YMRS). The results showed that serum TNF-α and IL-6 levels in manic, depressive and mixed state BD patients were significantly higher than that in controls, while serum IL-18 level was only significantly higher in depressive patients. Serum IL-6 level was significantly positively correlated with YMRS scores in manic episode as well as in mixed episode. When gender and age were added as potentially confounding covariate terms, the differences between controls and each mood state patients were still significant. Our findings provided additional evidence that elevated TNF-α, IL-6 and IL-18 pathway activities may be involved in the psychopathology of BD. Due to the lack of controlling important confounding factors, such as BMI, smoking status and alcohol use, further studies are required to confirm the roles of TNF-α, IL-6 and IL-18.

Hepatocyte transplantation (HTx) is a promising approach for the treatment of genetic liver diseases. However, the poor engrafted efficiency of 0.03-0.5% of transplanted cells in the recipient live...

Background Myelodysplastic syndromes (MDS) are clonal marrow stem-cell disorders with a high risk of progression to acute myeloid leukemia (AML). Treatment options are limited and targeted therapies are not available for MDS. In the present study, we investigated the cytotoxicity and the molecular mechanism of Homoharringtonine (HHT) and Bortezomib towards high-risk MDS cell line SKM-1 in vitro and the role of miR-3151 was first evaluated in SKM-1 cells. Methods SKM-1 cells were treated with different concentrations of HHT or Bortezomib, and cell viability was analyzed with CCK-8 assay. The influence on cell proliferation, cell cycle distribution and the percentage of apoptosis cells were analyzed by flow cytometry. Calcusyn software was used to calculate combination index (CI) values. Western blot was used to analysis phosphorylation of Akt and nuclear NF-κB protein expression in SKM-1 cells. Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. The cell proliferation and p53 protein level were reassessed in SKM-1 cells infected with lentivirus to overexpress miR-3151. Results Simultaneous exposure to HHT and Bortezomib (10.4:1) resulted in a significant reduction of cell proliferation in SKM-1 cells (P < 0.05). Cell cycle arrest at G0/G1 and G2/M phase was observed (P < 0.05). HHT and Bortezomib synergistically induced cell apoptosis by regulating members of caspase 9, caspase 3 and Bcl-2 family (P < 0.01). The mechanisms of the synergy involved Akt and NF-κB signaling pathway inhibition, downregulation of mature miR-3151 and increment of downstream p53 protein level. Overexpression of miR-3151 promoted cell proliferation and inhibited p53 protein expression in SKM-1 (P < 0.01). Conclusions HHT and Bortezomib synergistically inhibit SKM-1 cell proliferation and induce apoptosis in vitro. Inhibition of Akt and NF-κB pathway signaling contribute to molecular mechanism of HHT and Bortezomib. miR-3151 abundance is implicated in SKM-1 cell viability, cell proliferation and p53 protein expression.

Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses. We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-gamma, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.

Objective Studies of the effects of the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, ketamine, have suggested similarities to the symptoms of schizophrenia. Our primary goal was to evaluate the dimensions of the Positive and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic) compared to schizophrenia patients (early and chronic stages). Method We conducted exploratory factor analysis for the PANSS from four groups: 135 healthy subject administrated ketamine or saline, 187 inpatients of ketamine abuse; 154 inpatients of early course schizophrenia and 522 inpatients of chronic schizophrenia. Principal component factor analyses were conducted to identify the factor structure of the PANSS. Results Factor analysis yielded five factors for each group: positive, negative, cognitive, depressed, excitement or dissociation symptoms. The symptom dimensions in two schizophrenia groups were consistent with the established five-factor model (Wallwork et al., 2012). The factor structures across four groups were similar, with 19 of 30 symptoms loading on the same factor in at least 3 of 4 groups. The factors in the chronic ketamine group were more similar to the factors in the two schizophrenia groups rather than to the factors in the acute ketamine group. Symptom severities were significantly different across the groups (Kruskal–Wallis χ2(4) = 540.6, p

Ketamine is an increasingly popular drug of abuse in China but there is currently no method for classifying the psychological effects of ketamine in individuals with ketamine dependence.Develop a scale that characterizes the acute and long-term psychological effects of ketamine use among persons with ketamine dependence.We developed a preliminary symptom checklist with 35 dichotomous ('yes' or 'no') items about subjective feelings immediately after ketamine use and about perceived long-term effects of ketamine use that was administered to 187 inpatients with ketamine dependence recruited from two large hospitals in Guangzhou, China. Exploratory factor analysis (EFA) was conducted on a randomly selected half of thesample to reduce the items and to identify underlying constructs. Confirmatory factor analysis (CFA) was conducted on the second half of the sample to assess the robustness of the identified factor structure.Among the 35 symptoms, the most-reported acute effects were 'floating or circling' (94%), 'euphoric when listening to rousing music' (86%), and 'feeling excited, talkative, and full of energy' (67%). The mostreported long-term symptoms were 'memory impairment' (93%), 'personality changes' (86%), and 'slowed reactions' (81%). EFA resulted in a final 22-item scale best modelled by a four-factor model: two factors representing chronic symptoms (social withdrawal and sleep disturbances), one about acute psychoticlike symptoms, and one that combined acute drug-related euphoria and longer-term decreased libido. CFA showed that these 4 factors accounted for 50% of the total variance of the final 22-item scale and that the model fit was fair (Goodness of Fit Index, GIF=83.3%; Root Mean Square Error of Approximation, RMSEA=0.072).A four-factor model including social withdrawal, sleep disturbance, psychotic-like symptoms, and euphoria at the time of drug use provides a fair description of the short-term and long-term psychological symptoms associated with ketamine use. Future work on the 22-item version of the scale with larger samples is needed to confirm the validity of this 4-factor structure, to assess the scale's test-retest reliability, and to determine whether or not it can be useful in the differential diagnosis and monitoring of treatment of individuals with ketamine dependence.氯胺酮滥用在中国日渐增多，但目前还没有一个方法可以将氯胺酮对依赖个体的心理影响作用进行分类。.编制能反映氯胺酮依赖人群中因该物质滥用所致的急性心理影响和长期心理影响的量表。.我们编制了一个初步的症状清单，共有35个条目（“ 是” 或“ 否” 的二分法问题），内容是关于使用氯胺酮后即刻产生的主观感受以及氯胺酮滥用后感受到的长期作用。从中国广州市两个大医院招募氯胺酮依赖住院患者，共入组187例。随机选择一半的样本进行探索性因子分析(exploratory factor analysis, EFA)，以精简条目并确定量表的基本结构。对另一半样本进行验证性因子分析(confirmatory factor analysis, CFA)，以评估所提取因子结构的稳健性。.35个症状中常见的急性期症状是“ 身体的漂浮或盘旋感”（94％）、“ 在动感音乐的环境下心情更加舒畅、欣快感”（86％）、和“兴奋话多，精力充沛”（67％）。常见的慢性症状是“ 记忆力下降”（93％）、“ 性格变化”（86 ％） 和“反应变慢”（81 ％）。探索性因子分析最终得到的最佳模型量表，共22个条目，构成四个因子：两个因子代表慢性症状（社交退缩和睡眠障碍），一个因子是关于急性精神病样症状的，而第四个因子整合了急性的药物所致的欣快感和长期的性欲下降。验证性因素分析显示这4个因子能解释最终22个条目量表总方差的50％，并且模型拟合良好（拟合指数，GFI=83.3％；近似误差均方根，RMSEA=0.072）。.四因子模型（社交退缩、睡眠障碍、精神病样症状和使用毒品时的欣快感）能较为客观地反映氯胺酮滥用相关的短期和长期心理症状。对这一22个条目的量表，今后的研究工作需要扩大样本量，以验证实该四因子结构的效度，评估量表的重测信度，并确定是否能将该量表用于氯胺酮依赖的鉴别诊断和治疗监测。.本文全文中文版从2015年8月6日起在http://dx.doi.org/10.11919/j.issn.1002-0829.214158可供免费阅览下载.

Itch is a common symptom of diseases of the skin but can also accompany diseases of other tissues including the nervous system. Acute itch from chemicals experimentally applied to the skin is initiated and maintained by action potential activity in a subset of nociceptive neurons. But whether these pruriceptive neurons are active or might become intrinsically more excitable under the pathological conditions that produce persistent itch and nociceptive sensations in humans is largely unexplored. Recently, two distinct types of cutaneous nociceptive dorsal root ganglion neurons were identified as responding to pruritic chemicals and playing a role in itch sensation. One expressed the mas-related G-coupled protein receptor MRGPRA3 and the other MRGPRD (MRGPRA3+ and MRGPRD+ neurons, respectively). Here we tested whether these two distinct pruriceptive nociceptors exhibited an enhanced excitability after the development of contact hypersensitivity, an animal model of allergic contact dermatitis, a common pruritic disorder in humans. The characteristics of increased excitability of pruriceptive neurons during this disorder may also pertain to the same types of neurons active in other pruritic diseases or pathologies that affect the nervous system and other tissues or organs. We found that challenging the skin of the calf of the hind paw or the cheek of previously sensitized mice with the hapten, squaric acid dibutyl ester, produced symptoms of contact hypersensitivity including an increase in skin thickness and site-directed spontaneous pain-like (licking or wiping) and itch-like (biting or scratching) behaviours. Ablation of MRGPRA3+ neurons led to a significant reduction in spontaneous scratching of the hapten-challenged nape of the neck of previously sensitized mice. In vivo, electrophysiological recordings revealed that MRGPRA3+ and MRGPRD+ neurons innervating the hapten-challenged skin exhibited a greater incidence of spontaneous activity and/or abnormal after-discharges in response to mechanical and heat stimuli applied to their receptive fields compared with neurons from the vehicle-treated control animals. Whole-cell recordings in vitro showed that both MRGPRA3+ and MRGPRD+ neurons from hapten-challenged mice displayed a significantly more depolarized resting membrane potential, decreased rheobase, and greater number of action potentials at twice rheobase compared with neurons from vehicle controls. These signs of neuronal hyperexcitability were associated with a significant increase in the peak amplitude of tetrodotoxin-sensitive and resistant sodium currents. Thus, the hyperexcitability of MRGPRA3+ and MRGPRD+ neurons, brought about in part by enhanced sodium currents, may contribute to the spontaneous itch- and pain-related behaviours accompanying contact hypersensitivity and/or other inflammatory diseases in humans.

This study investigated the serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in a group of chronic ketamine abusers in comparison to healthy controls. The correlations between the serum BDNF, NGF level with the subjects' demographic, pattern of ketamine use were also examined.93 subjects who met the criteria of ketamine dependence and 39 healthy subjects were recruited. Serum BDNF and NGF levels were assayed by enzyme-linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).Both serum levels of BDNF and NGF were significant lower in the ketamine users compared to the healthy control subjects (9.50±6.68 versus 14.37±6.07 ng/ml, p=0.019 for BDNF; 1.93±0.80 versus 2.60±1.07 ng/ml, p=0.011 for NGF). BDNF level was negatively associated with current frequency of ketamine use (r=-0.209, p=0.045).Both BDNF and NGF serum concentrations were significantly lower among chronic ketamine users than among health controls.

6-Aminohexyl alpha-D-galactopyranosyl-(1--4)-beta-D-galactopyranosyl-(1--4)-beta-D-glucopyranoside (2), a globotriose analogue with a functionalized aglycon, was synthesized, using alpha-D-galactopyranosyluronic acid-(1--4)-D-galactopyranosyluronic acid [di-GalA (3)] as the starting material, which is commercially available or can be readily prepared from pectin.

Summary Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ 9 -tetrahydrocannabinol (Δ 9 -THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ 9 -THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ 9 -THC exposures. Ablation of COX-2 also eliminates Δ 9 -THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ 9 -THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.

Glycosylations and deacetylations of 2-O-acetyl of O-peracetylated β-D-glucopyranose were realized in one step by reactions with 4.0 equivalents of alcohols and 1.5 equivalents of trifluoroborane etherate. Thus, various β-D-glucopyranosides with a free hydroxyl group on C-2 were conveniently prepared and applied for synthesis of Glcl → 2 linked disaccharides. On leave from Department of Chemistry, Jiangxi Normal University, Nanchang330027, China.

Background and purpose The data concerning the association between environmental pollution and epilepsy attacks are limited. The aim of this study was to explore the association between acute air pollution exposure and epilepsy attack. Methods A hospital record-based study was carried out in Xi’an, a heavily-polluted metropolis in China. Daily baseline data were obtained. Time-series Poisson regression models were applied to analyze the association between air pollution and epilepsy. Results A 10 μg/m3 increase of NO2, SO2, and O3 concentrations corresponded to 3.17% (95%Cl: 1.41%, 4.93%), 3.55% (95%Cl: 1.93%, 5.18%), and -0.84% (95%Cl: -1.58%, 0.09%) increase in outpatient-visits for epilepsy on the concurrent days, which were significantly influenced by sex and age. The effects of NO2 and SO2 would be stronger when adjusted for PM2.5. As for O3, a -1.14% (95%Cl: -1.90%, -0.39%) decrease was evidenced when adjusted for NO2. The lag models showed that the most significant effects were evidenced on concurrent days. Conclusions We discovered previously undocumented relationships between short-term air pollution exposure and epilepsy: while NO2 and SO2 were positively associated with outpatient-visits of epilepsy, O3 might be associated with reduced risk.

For many patients with psychiatric disorders, the course of illness is characterized by frequent relapses, resulting to re-hospitalization and high costs. While the correlates of readmission have been extensively studied in developed countries, few studies have examined readmission in low- and middle-income countries where bed supply is limited.Using administrative data from the Guangzhou Psychiatric Hospital (GPH), we used Cox regression models to evaluate the relationship among age, gender, index length of stay (LOS), and the number of previous admissions to post-discharge readmission risk. Linear regression is used to evaluate predictors of total hospital days during the year after the index discharge.Between April 1, 2010 and March 31, 2011, 2,525 patients were discharged with International Classification of Diseases, 10th Revision psychiatric diagnoses from GPH, with an average LOS of 64.2 (SD = 69.0), and 317 (12.4%) were readmitted in the following year. Survival analysis showed older age (P 0.05), and the number of previous hospitalizations (P 0.01) were significant predictors of the risk of readmission but not diagnosis or LOS. The number of previous admissions was the only predictor of total bed days of psychiatric care at GPH in the year following the initial discharge.Shortened LOS was not associated with increased readmission risk or post-discharge hospital days. Rather, the number of past hospitalizations was the major predictor of both readmission risk and post-discharge hospital days of psychiatric care, and such patients deserve special attention. Lowering LOS may be justified, allowing funds to be redeployed to outpatient or community-based care.

The level and integrity of glutamate transmission during critical periods of postnatal development plays an important role in the refinement of pyramidal neuron dendritic arbor, synaptic plasticity, and cognition. Presently, it is not clear how excitatory transmission via the two predominant isoforms of the vesicular glutamate transporter (VGLUT1 and VGLUT2) participate in this process. To assess a neurodevelopmental role for VGLUT2 in pyramidal neuron maturation, we generated recombinant VGLUT2 knock-out mice and inactivated VGLUT2 throughout development using Emx1-Cre+/+knock-in mice. We show that VGLUT2 deficiency in corticolimbic circuits results in reduced evoked glutamate transmission, release probability, and LTD at hippocampal CA3-CA1 synapses during a formative developmental period (postnatal days 11–14). In adults, we find a marked reduction in the amount of dendritic arbor across the span of the dendritic tree of CA1 pyramidal neurons and reduced long-term potentiation and levels of synaptic markers spinophilin and VGLUT1. Loss of dendritic arbor is accompanied by corresponding reductions in the number of dendritic spines, suggesting widespread alterations in synaptic connectivity. Conditional VGLUT2 knock-out mice exhibit increased open-field exploratory activity yet impaired spatial learning and memory, endophenotypes similar to those of NMDA receptor knock-down mice. Remarkably, the impairment in learning can be partially restored by selectively increasing NMDA receptor-mediated glutamate transmission in adult mice by prolonged treatment withd-serine and ad-amino acid oxidase inhibitor. Our data indicate that VGLUT2 expression is pivotal to the proper development of mature pyramidal neuronal architecture and plasticity, and that such glutamatergic deficiency leads to cognitive malfunction as observed in several neurodevelopmental psychiatric disorders.

The aim of this study was to quantify the oral delivery systems of Tetramethylpyrazine Microemulsion (TMP ME) to heart, liver, spleen, lung, kidney and brain by comparing TMP level after oral administration at a dose of 100 mg kg(-1) with those of TMP tablet suspension (TMP SWW). This study was taken in mice to develop a suitable analytical methodology in pharmacokinetics studies and to manipulate the tissue distribution and targeting evaluation. Drug concentrations in tissues were determined at different times post-mortem. An HPLC method for separation and quantification of TMP was developed and validated by studying mice tissues. Following oral administration, TMP concentrations in different tissues were constantly detected for quite a long time and finally differed significantly from each other. The AUC rank order 3 of ME group is AUCliver > AUCbrain > AUClung > AUCspleen > AUCheart > AUCkidney, while the SWW group is AUCliver > AUClung > AUCspleen > AUCheart > AUCbrain > AUCspleen. Especially, the AUC value in brain region (AUCbrain) of ME is 6.06-fold of SWW. The drug relative overall targeting efficiency (RTE) are calculated: heart (7.49%), liver (3.54%), spleen (12.60%), lung (6.02%), kidney (2.86%) and brain (12.51%). The results from ME directly showed obvious targeting transport to the brain. These results indicated that this new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.

Chronic compression (CCD) of the dorsal root ganglion (DRG) is a model of human radicular pain produced by intraforaminal stenosis and other disorders affecting the DRG, spinal nerve, or root. Previously, we examined electrophysiological changes in small-diameter lumbar level 3 (L3) and L4 DRG neurons treated with CCD; the present study extends these observations to medium-sized DRG neurons, which mediate additional sensory modalities, both nociceptive and non-nociceptive. Whole-cell patch-clamp recordings were obtained from medium-sized somata in the intact DRG in vitro. Compared with neurons from unoperated control animals, CCD neurons exhibited a decrease in the current threshold for action potential generation. In the CCD group, current densities of TTX-resistant and TTX-sensitive Na+ current were increased, whereas the density of delayed rectifier voltage-dependent K+ current was decreased. No change was observed in the transient or “A” current after CCD. We conclude that CCD in the mouse produces hyperexcitability in medium-sized DRG neurons, and the hyperexcitability is associated with an increased density of Na+ current and a decreased density of delayed rectifier voltage-dependent K+ current.

To research the disperse behavior of many Chinese medicine decoctions.Through the analysis of the dispersible attributes of 22 kinds of Chinese medicine decoctions including Radix Salviae Miltiorrhizae by means of turbidity, ultramicroscope and TEM, we found that a lot of nanometer particles existed in these decoctions after 4000 r/min centrifugation. Based on the model of Radix Salviae Miltiorrhizae, we analyzed the influence on the loss of effective ingredients by way of centrifugation, alcohol precipitation, flocculation and salting-out edulcoration.The removal of infinite nanometer particles from these decoctions led to the greater loss of water-soluble and fat-soluble ingredients,and the latter accounts for the major loss.Oral liquid preparation of traditional Chinese medicine is a kind of nano-pharmaceutics with nanometer particles dispersed in the water as the carriers of effective ingredients in medicine.

On the basis of a comprehensive study of the cyberword, this article puts emphasis on the exploration towards the characteristics, the commercial value and usage of the category which holds a context. In the end, this article indicates the problems within the commercial usage of the cyberword and gives related suggestions.

We investigated the effects of chronic compression (CCD) of the L3 and L4 dorsal root ganglion (DRG) on pain behavior in the mouse and on the electrophysiological properties of the small-diameter neuronal cell bodies in the intact ganglion. CCD is a model of human radicular pain produced by intraforaminal stenosis and other disorders affecting the DRG, spinal nerve, or root. On days 1, 3, 5, and 7 after the onset of compression, there was a significant decrease from preoperative values in the threshold mechanical force required to elicit a withdrawal of the foot ipsilateral to the CCD (tactile allodynia). Whole cell patch-clamp recordings were obtained, in vitro, from small-sized somata and, for the first time, in the intact DRG. Under current clamp, CCD neurons exhibited a significantly lower rheobase compared with controls. A few CCD but no control neurons exhibited spontaneous action potentials. CCD neurons showed an increase in the density of TTX-resistant and TTX-sensitive Na+ current. CCD neurons also exhibited an enhanced density of voltage-dependent K+ current, due to an increase in delayed rectifier K+ current, without a change in the transient or “A” current. We conclude that CCD in the mouse produces a model of radicular pain, as we have previously demonstrated in the rat. While the role of enhanced K+ current remains to be elucidated, we speculate that it represents a compensatory neuronal response to reduce ectopic or aberrant levels of neuronal activity produced by the injury.

The purpose of this study was to explore the effect of proteasome inhibitor, bortezomib (Bzb), on osteoblast in pathologic status of myeloma bone disease. The myeloma bone disease was modeled by co-culture of mouse myeloma cell RPMI8226 with osteoblast line MC-3T3E1 from mouse calvaria, and intervenient culture of supernatant. The inhibitory effect of Bzb on proliferation of MC-3T3E1 assayed by modified MTT method, the apoptosis of MC-3T3E1 cells was determined by flow cytometry with Annexin V/PI staining, the expressions of osteoblast markers, Runx2/cbfa1, osteocalcin (OCN) and osterix (OSX) in MC-3T3E1 treated with Bzb were detected by RT-PCR and Western blot respectively. Experiments were divided into 3 group: single cultured, co-cultured and supernatant-interveniently cultured groups. The results showed the Bzb in higher concentration inhibited proliferation of MC-3T3E1 cells in a dose-dependent manner, with the IC(50) of 38.1 nmol/L for 48 hours, the Bzb in low concentration (5 nmol/L) did not show the inhibitory effect on proliferation of MC-3T3E1 in single cultured group (p0.10), but could decrease apoptotic rate of MC-3T3E1 by 32.5% and 24.6% respectively in cocultured and supernatant-interveniently cultured groups, moreover increased the expression of osteoblast-related gene OSX, OCN mRNA and protein (p0.05), while no obvious change of Runx2/cbfa1 expression was observed (p0.05). It is concluded that the proteasome inhibitor, Bzb, in low concentration promotes the activity of osteoblast internal mechanisms, and prevents the apoptosis of osteoblasts induced by myeloma cells. In addition, it can up-regulate transcription and expression of osteoblast markers related to Runx2/cbfa1 path way, thus may protect osteoblasts in myeloma bone disease.

As the genomic basis for Down syndrome (DS), human trisomy 21 is the most common genetic cause of intellectual disability in children and young people. The genomic regions on human chromosome 21 (Hsa21) are syntenic to three regions in the mouse genome, located on mouse chromosome 10 (Mmu10), Mmu16, and Mmu17. Recently, we have developed three new mouse models using chromosome engineering carrying the genotypes of Dp(10)1Yey/+, Dp(16)1Yey/+, or Dp(17)1Yey/+, which harbor a duplication spanning the entire Hsa21 syntenic region on Mmu10, Mmu16, or Mmu17, respectively. In this study, we analyzed the hippocampal long-term potentiation (LTP) and cognitive behaviors of these models. Our results show that, while the genotype of Dp(17)1Yey/+ results in abnormal hippocampal LTP, the genotype of Dp(16)1Yey/+ leads to both abnormal hippocampal LTP and impaired learning/memory. Therefore, these mutant mice can serve as powerful tools for further understanding the mechanism underlying cognitively relevant phenotypes associated with DS, particularly the impacts of different syntenic regions on these phenotypes.

Glycosylations and deacetylations of 2-O-acetyl of O-peracetylated β-D-glucopyranose were realized in one step by reactions with 4.0 equivalents of alcohols and 1.5 equivalents of trifluoroborane etherate. Thus, various β-D-glucopyranosides with a free hydroxyl group on C-2 were conveniently prepared and applied for synthesis of Glcl → 2 linked disaccharides. On leave from Department of Chemistry, Jiangxi Normal University, Nanchang330027, China.

Two series of aromatic copolyesters with flexible spacers were prepared by solution polycondensation of terephtalates, aromatic diols (hydroquinone or methylhydroquinone) and 2,5-dicholroterephtaloyl chloride. Both series show a melting point mesophase stable over a broad temperature range.

To investigate the long-term clinical outcomes of porcelain laminate veneers 1-8 years following delivery.A total of 310 feldspathic porcelain laminate veneers on anterior teeth or premolars in 49 patients were included in the present study 1-8 years following delivery. All the subjects underwent a detailed clinical examination utilizing modified United States Public Health Service (USPHS) criteria. Restoration integrity, abrasion, color satisfaction, marginal discoloration, marginal adaptation, secondary caries, postoperative sensitivity, and gingival index (GI) of the prostheses were evaluated according to modified USPHS criteria. The 1-8 year survival rates of the veneers were statistically analyzed using the life table method.The survival rates of porcelain laminate veneers were 98.7%, 98.0%, 93.8%, 93.2%, 89.7%, 81.8%, 76.3%, and 76.3% in 1 to 8 years, respectively.The long-term clinical outcomes of porcelain laminate veneers are satisfying.

Chronic use of marijuana impairs synaptic plasticity and cognitive function. However, the molecular mechanisms by which marijuana alters long-term synaptic plasticity are largely unknown. Here, we show that repeated in vivo exposures to Delta9-THC for 7 consecutive days significantly impaired hippocampal long-term potentiation (LTP) of excitatory glutamatergic synaptic transmission. The Delta9-THC exposure-induced decrease in LTP was prevented by pharmacological inhibition or deletion of the cannabinoid 1 receptor (CB1R). To determine the molecular mechanisms underlying Delta9-THC-altered LTP, we targeted expression and function of the glutamate receptors (GluR) and phosphorylation status of cAMP-response element-binding protein (CREB). Chronic in vivo exposure to Delta9-THC produced CB1R-dependent decreases in expression of hippocampal GluR1, NR2A, and NR2B, the ratio of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/NMDA receptor-gated currents, and phosphorylation of CREB. Our results suggest that reduced expression and function of the GluR subunits and phosphorylation of CREB may underlie the impaired long-term synaptic plasticity induced by repeated in vivo exposure to Delta9-THC.

The best absorption location of puerarin microemulsion-in-oil in intestine parva of rat and pharmacokinetic characteristics, and the pathway of absorption and conveying of puerarin microemulsion were studied. In situ rat perfusion method was used to investigate the intestinal absorption of puerarin. Through the changes of drug concentration in blocked and unblocked lymphs, to determine the pathway of absorption and conveying. Puerarin microemulsion-in-oil can be absorbed in any part of intestine, and the K(a), P(app) of every part is ileumduodenumjejunumcolon, and the K(a), P(app) of ileum is significantly larger than that of others. The absorption rate of different concentrations is not significantly different (P0.05). The puerarin transited by gastrointestinal tract, about 36.8% is absorbed by the lymphatic channels to enter the systemic circulation and 63.2% is absorbed by the non-lymphatic channels. The best part of intestine to absorb puerarin microemulsion is ileum, and it is passive transport. The pathway of conveying is lymphoid and non-lymphoid transit.