Association of body mass index with rapid eye movement sleep behavior disorder in Parkinson's disease.

Background: The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson's disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients. Methods: In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson's Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models. Results: We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results. Conclusion: The current study found a significant dose-response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers.

Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.

Serum exosomal hsa_circRNA_0001842 is the potential biomarker for diagnosing lower limb vascular disease in type 2 diabetes mellitus.

This study aimed to identify the potential circular RNAs (circRNAs) in exosomes isolated from serum as biomarkers of lower limb vascular disease (LLVD) in patients with type 2 diabetes mellitus (T2DM). This research collected circRNAs from exosomes isolated from three T2DM patients and three T2DM patients with LLVD for microarray analysis. Five candidate biomarkers derived from differentially expressed circRNAs were then validated by quantitative real-time polymerase chain reaction in 20 T2DM patients and 20 T2DM patients with LLVD. Finally, expression levels of circRNAs were validated in 160 samples. Significant differences in the expression of 295 circRNAs were found between T2DM controls and T2DM patients with LLVD. Among them, 191 differentially expressed circRNAs were upregulated, and 104 were downregulated in T2DM patients with LLVD. Three upregulated and two downregulated circRNAs were further confirmed in 40 samples. According to the testing of 160 samples, hsa_circ_0001842 showed a noticeable specificity in the T2DM patients with LLVD group (n = 80), with an area under the curve (AUC) of 0.79, a sensitivity of 88.75%, and a specificity of 68.75%. In conclusion, hsa_circ_0001842 was found as a potential diagnostic biomarker for T2DM with LLVD.

PPARα is involved in high-fat diet-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Risk avoidance behaviors are essential for survival. "Uncontrollable" risk-taking behaviors in animals or humans may have severe adverse consequences. In humans, a large proportion of psychiatric disorders are accompanied by impairments in risk avoidance. Obesity is associated with psychiatric disorders. Peroxisome proliferator-activated receptor α (PPARα) takes part in regulating lipid metabolism and neuronal function. Here, we investigated the effect of high-fat diet (HFD)-induced obesity on risk avoidance and the role of PPARα in this behavior. Male PPARα-null (KO) mice and wild-type (WT) mice were assigned to four different groups: WT-CON and KO-CON (normal diet); WT-HFD and KO-HFD (high fat diet). The HFD began at week 6 and was continued until sampling. A series of behavioral tests were performed at week 11. We found that WT but not KO mice fed with a HFD exhibited weight gain and risk avoidance impairment, compared with the mice fed with a normal diet. The staining of c-Fos revealed that the hippocampus was the main brain region involved in risk avoidance behavior. Moreover, biochemical analysis suggested that the decreased levels of the brain-derived neurotrophic factor (BDNF) in the hippocampus might contribute to risk avoidance impairment induced by a HFD. These results indicated that PPARα is involved in HFD-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Lateral septal nucleus, dorsal part, and dentate gyrus are necessary for spatial and object recognition memory, respectively, in mice.

Introduction: Cognitive impairment includes the abnormality of learning, memory and judgment, resulting in severe learning and memory impairment and social activity impairment, which greatly affects the life quality of individuals. However, the specific mechanisms underlying cognitive impairment in different behavioral paradigms remain to be elucidated. Methods: The study utilized two behavioral paradigms, novel location recognition (NLR) and novel object recognition (NOR), to investigate the brain regions involved in cognitive function. These tests comprised two phases: mice were presented with two identical objects for familiarization during the training phase, and a novel (experiment) or familiar (control) object/location was presented during testing. Immunostaining quantification of c-Fos, an immediate early gene used as a neuronal activity marker, was performed in eight different brain regions after the NLR or NOR test. Results: The number of c-Fos-positive cells was significantly higher in the dorsal part of the lateral septal nucleus (LSD) in the NLR and dentate gyrus (DG) in the NOR experiment group than in the control group. We further bilaterally lesioned these regions using excitotoxic ibotenic acid and replenished the damaged areas using an antisense oligonucleotide (ASO) strategy. Discussion: These data reinforced the importance of LSD and DG in regulating spatial and object recognition memory, respectively. Thus, the study provides insight into the roles of these brain regions and suggests potential intervention targets for impaired spatial and object recognition memory.

[Effects of Acrolein on the Proliferation of and Per1 Gene Expression in Pulmonary Epithelial Cells].

OBJECTIVE: To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism. METHODS: Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 µmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 ( Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-ß (TGF-ß) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined. RESULTS: The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 µmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly ( P<0.05). The addition of TGF-ß after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-ß ( P<0.05). CONCLUSION: Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-ß addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-ß after acrolein treatment.

Comparison of botulinum toxin with surgery for the treatment of acute acquired comitant esotropia and its clinical characteristics.

We compared the therapeutic effects between botulinum toxin and surgery for acute acquired comitant esotropia (AACE) and analyze its clinical characteristics. The data of the 29 cases, who received treatment for AACE in the Ophthalmic Center of the First Affiliated Hospital of Zhengzhou University and Henan Provincial Ophthalmology Hospital between January 2016 and January 2017, were collected. The 29 cases with AACE were followed for 6 months or more, and received either botulinum toxin injection (group A with 13 cases) or squint correction (group B with 16 cases). The distant and near deviation angles were compared between the two groups before and after treatment. The success rate (total horizontal deviation of 10 prism diopters or less) and stereopsis were compared between the two groups at post-treatment 6 months. At the same time, the relations between distant and near deviation angles were analyzed among different myopia levels and different AACE types. Results indicated that he success rate was not significantly different at post-treatment 6 months (84.6% vs 81.3%, P = 1.00). The distant and near deviation angles were all significantly different one day and one month after treatment (all P < 0.05); but at post-treatment 6 months, they were not significantly different (all P > 0.05) between the two groups. There were no significant differences in the distant and near stereoacuity between the two groups at post-treatment 6 months (all P > 0.05). Among the 25 cases with myopia, the pre-treatment distant deviation angle was significantly higher than pre-treatment near deviation angle in the cases with myopia level >-2.5 D (P < 0.05), and the pre-treatment distant and near deviation angles were all significantly higher in the cases with type-IIAACE than in the cases with type-IIIAACE (all P < 0.05). This study suggests that Botulinum toxin is as effective as surgery in the treatment of AACE at post-treatment 6 months. For the cases with myopia level >-2.5 D, the pre-treatment distant deviation angle is significantly higher than pre-treatment near deviation angle; and both pre-treatment distant and near deviation angles are greater in the cases with type-IIAACE than in the cases with type-IIIAACE.

Over-expression of the long non-coding RNA HOTTIP inhibits glioma cell growth by BRE.

BACKGROUND: Gliomas are the most common type of primary brain tumour in the central nervous system of adults. The long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) is transcribed from the 5' tip of the HOXA locus. HOTTIP has recently been shown to be dysregulated and play an important role in the progression of several cancers. However, little is known about whether and how HOTTIP regulates glioma development. METHODS: In this study, we assayed the expression of HOTTIP in glioma tissue samples and glioma cell lines using real-time polymerase chain reaction and defined the biological functions of HOTTIP using the CCK-8 assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay) and tumour formation assay in a nude mouse model. Finally, we discovered the underlying mechanism using the Apoptosis PCR 384HT Array, Western blot, RNA immunoprecipitation (RIP) and luciferase reporter assay. RESULTS: HOTTIP was aberrantly down-regulated in glioma tissues and glioma cell lines (U87-MG, U118-MG, U251 and A172), and over-expression of HOTTIP inhibited the growth of glioma cell lines in vitro and in vivo. Furthermore, HOTTIP could directly bind to the brain and reproductive expression (BRE) gene and down-regulate BRE gene expression. In addition, we further verified that over-expression of the BRE gene promoted the growth of glioma cell lines in vitro. Finally, over-expression of HOTTIP significantly suppressed the expression of the cyclin A and CDK2 proteins and increased the expression of the P53 protein. However, we found that the over-expression of BRE significantly increased the expression of the cyclin A and CDK2 proteins and suppressed the expression of the P53 protein. Taken together, these findings suggested that high levels of HOTTIP reduced glioma cell growth. Additionally, the mechanism of HOTTIP-mediated reduction of glioma cell growth may involve the suppression of cyclin A and CDK2 protein expression, which increases P53 protein expression via the down-regulation of BRE. CONCLUSIONS: Our studies demonstrated that over-expression of HOTTIP promotes cell apoptosis and inhibits cell growth in U118-MG and U87-MG human glioma cell lines by down-regulating BRE expression to regulate the expression of P53, CDK2 and Cyclin A proteins. The data described in this study indicate that HOTTIP is an interesting candidate for further functional studies in glioma and demonstrate the potential application of HOTTIP in glioma therapy.

Erratum to "Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom".

[This corrects the article DOI: 10.1155/2014/621756.].

Celastrol Ameliorates EAE Induction by Suppressing Pathogenic T Cell Responses in the Peripheral and Central Nervous Systems.

Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disease of the central nervous system (CNS), and MS results in physical and cognitive impairments, such as fatigue, pain, depression and bladder dysfunction. Though many therapies for MS have been developed, the safety profile and effectiveness of these therapies still need to be defined. Thus, new therapies for MS must be explored. Celastrol, a quinonemethide triterpene, is a pharmacologically active compound present in Thunder God Vine root extracts used to treat inflammatory and autoimmune diseases. Molecular studies have identified several molecular targets, which are mostly centered on the inhibition of IKK-NF-κB signaling. The animal model of experimental autoimmune encephalomyelitis (EAE) has been widely used in MS studies; thus, we tried to explore the role of celastrol in EAE development in this study. We demonstrated that the intraperitoneal injection of celastrol significantly attenuated EAE disease. Th17 cell responses in the peripheral lymph nodes in EAE mice were also inhibited by celastrol. We determined that celastroldownregulated cytokine production in bone-marrow derived dendritic cells (BMDCs). Accordingly, T cells that were co-cultured with either BMDCs pre-treated with celastrolor splenic DCs and then collected on day 7 after EAE immunizationshowed that Th17 cell polarization is suppressed in the above two situations. Moreover, celastrol was required for tissue-infiltrating DCs to sustain Th17 responses in the central nervous system (CNS). Taken together, the results of our study demonstrate that celastrol ameliorates EAE development by suppressing pathogenic Th17 responses; this finding offers a better understanding of the role of celastrol in EAE development as well as new proposals for clinical interventions.

Upregulation of miR-1280 expression in non-small cell lung cancer tissues.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prolific and high-mortality disease with few effective treatments. Although the detection and surgical techniques for NSCLC continue to advance, the survival rate for the patients with NSCLC remains poor. Enhanced predictive biomarkers such as microRNAs (miRNAs) are needed at the time of diagnosis to better tailor therapies for patients. This study focused on the expression of miR-1280 in NSCLC tissues and distal normal tissues in order to explore the association between miR-1280 expression and NSCLC. METHODS: A total of 72 newly diagnosed primary NSCLC patients were enrolled in this study. Quantitative real-time polymerase chain reaction (PCR) was performed to identify the expression level of miR-1280 in the NSCLC tissues and distal normal tissues of these patients. RESULTS: The miR-1280 expression was significantly higher in the NSCLC tissues (0.084 ± 0.099) than distal normal tissues (0.014 ± 0.015, P = 0.009). In 54 patients (75%), the miR-1280 expression in the NSCLC tissues was upregulated (2-ΔΔct > 2), and no case showed a downregulation of miR-1280 expression. CONCLUSIONS: The expression level of miR-1280 could be regarded as a biomarker for NSCLC.

[Analysis on medication principles for cough based on experience of Xu Di-hua, descendant of Meng He Medical School].

Based on the software of traditional Chinese medicine inheritance support system (TCMISS), this article aims to analyze the experience and composition rules for cough from the descendant of Meng He Medical School, Xu Di-hua. The cough cases treated by Xu Di-hua were collected, and recorded into TCMISS (V2.0). Data mining methods such as Apriori algorithm and complex system entropy cluster were used to analyze the medication principles of Xu Di-hua for cough from pathogenesis and therapeutie aspects, and dig out the frequency of the herbs in prescription, core medicine and new combinations. The experience of curing cough from Professor Xu Di-hua were well found in the research. He is good at choosing prescriptions accurately, and pays attention to simultaneous use of cold and moisture drugs with combination of tonification and purgation. He is skilled in adding or reducing materia medica flexibly, as well as regulating lung to relieve cough and eliminating phlegm by clearing heat.

Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-α and ICAM-1 levels while preserving differentiation in ATRA-induced acute promyelocytic leukemia cells.

All-trans retinoic acid (ATRA) is a revolutionary agent for acute promyelocytic leukemia (APL) treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1) expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS) which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1ß secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy.

Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom.

Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 µ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

High-resolution reconstruction for terahertz imaging.

We present a high-resolution (HR) reconstruction model and algorithms for terahertz imaging, taking advantage of super-resolution methodology and algorithms. The algorithms used include projection onto a convex sets approach, iterative backprojection approach, Lucy-Richardson iteration, and 2D wavelet decomposition reconstruction. Using the first two HR reconstruction methods, we successfully obtain HR terahertz images with improved definition and lower noise from four low-resolution (LR) 22×24 terahertz images taken from our homemade THz-TDS system at the same experimental conditions with 1.0 mm pixel. Using the last two HR reconstruction methods, we transform one relatively LR terahertz image to a HR terahertz image with decreased noise. This indicates potential application of HR reconstruction methods in terahertz imaging with pulsed and continuous wave terahertz sources.

IP-FCM platform detects the existence and regulator-caused dissociation of components in naturally assembled HSP90 complex.

Flow cytometry, in conjunction with immunoprecipitation (IP-FCM), is suggested to have some advantages to conventional IP-western blot technology in analyzing protein complexes. In this paper, to further examine its practicability, we test the use of IP-FCM in detecting the HSP90 complex, which has gained importance in drug research and development and involves more than a dozen components. We found that IP-FCM could effectively detect HSP70, p23, Cdc37, and Cdk6 components in the HSP90 complex naturally formed in U937 cells when this complex was captured by anti-HSP90 antibody-coated polystyrene microspheres. IP-FCM could also detect alteration in components caused by treating cells with HSP90 inhibitors. In a cell-free environment, IP-FCM could detect the direct effects of ATP and/or HSP90 inhibitors (17-N-allylamino-17-demethoxygeldanamycin or celastrol) in causing component dissociation and the time- and dose-effects of inhibitor-caused dissociation. IP-FCM is a practical and powerful platform for analyzing HSP90 complex components, and is thus a useful tool in studying HSP90 complex function and screening inhibitors.

[Study on THz spectra and vibrational modes of benzoic acid and sodium Benzoate].

Terahertz time-domain spectroscopy was employed to measure the terahertz absorption spectra of benzoic acid and sodium benzoate at room temperature. The origins of the measured features of benzoic acid were summarized based on previous study. Density functional theory was used to compute and analyze the molecular structure and vibrational modes of sodium benzoate in monomer. Based on the obtained results, the authors found that the THz spectral features can be used to distinguish benzoic acid and sodium benzoate totally; the essential reason for the THz spectral difference between benzoic acid and sodium benzoate is that the electrovalent bond of sodium benzoate affects the values of covalent bond lengths and bond angles, as well as the molecular interactions and arrangement in unit cell; the measured features of benzoic acid and sodium benzoate come from the collective vibrations except the peaks located at 107 cm-1 of benzoic acid and 54 cm-1 of sodium benzoate.

Fixational saccadic eye movements are altered in anisometropic amblyopia.

PURPOSE: Amblyopia develops during a critical period in early visual development and is characterized by reduced visual sensory functions and structural reorganization of the brain. However, little is known about oculomotor functions in amblyopes despite the special role of eye movements in visual perception, task execution and fixation. Therefore, we studied the relationship of visual deficits in anisometropic amblyopia and fixational saccadic eye movements. METHODS: We recruited twenty-eight anisometropic amblyopes and twenty-eight age-matched control subjects. Using a high-speed eye-tracker, fixational eye-movements of both eyes were recorded. A computerized fixational saccadic component analysis of eye-movement waveforms was developed to quantify the parameters of fixational saccades (FSs) and a simulation model was developed to help explain the FS performances. RESULTS: Amblyopic eyes, but not control eyes, showed fewer FSs, but these had increased amplitudes, increased peak velocities, and longer inter-saccadic intervals. The reduced FSs occurred mainly in the 0- to 0.6-degree amplitude range, and the probability of FSs with larger amplitudes and longer inter-saccadic intervals was significantly higher than in controls. A new simulation model analysis suggests that an excitatory-inhibitory activity imbalance in superior colliculus may explain these FSs changes. CONCLUSIONS: We propose that the abnormal visual processing and circuitry reorganization in anisometropic amblyopia has an impact on the fixational saccade generation. We see two possible interpretations: (i) altered FSs may be an attempt of the visual system to adapt to the deficit, trying to capture more information from a broader spatial domain of the visual world so as to enhance the contrast sensitivity to low spatial frequencies viewed by the amblyopic eye, or (ii) it may be the cause of amblyopia or a contributing factor to the original deficit that aggravates the early deprivation.