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Functional staple food is the trend of industrialization of staple food in our country. It is an important way to make staple food with some specific functions.The physicochemical properties and HMG-CoA inhibition of extruded rice with red yeast rice flour (RYRF) addition were investigated. Results showed that RYRF addition was beneficial to produce hypolipidemic functional staple foods from extruded rice, involving in color, short-range order, HMG-CoA inhibition, porosity, crystallinity, and mass loss. These were mainly attributed to the biochemical reaction of RYRF which could inhibit the recrystallization of amylopectin and HMG-CoA reductase activity. Among the five concentrations of RYRF additives (0.5%, 1.0%, 2.0%, 3.0%, 4.0% w/w), the extruded rice with 3% RYRF addition achieved the best data in terms of porosity, crystallinity, mass loss and HMG-CoA inhibition rate. [Display omitted] • The red yeast rice flour (RYRF) improved the quality and function of extruded rice. • The RYRF inhibited recrystallization of amylopectin and HMG-Co A reductase activity. • The study provides a new idea for the application of red yeast in functional food. [ABSTRACT FROM AUTHOR]

The retinopathy of prematurity (ROP) can cause serious clinical consequences and, fortunately, it is remediable while the time window for treatment is relatively narrow. Therefore, it is urgent to screen all premature infants and diagnose ROP degree timely, which has become a large workload for pediatric ophthalmologists. We developed a retinal image-free procedure using small amount of blood samples based on the plasma Raman spectrum with the machine learning model to automatically classify ROP cases before medical intervention was performed. Statistical differences in infrared Raman spectra of plasma samples were found among the control, mild (ZIIIS1), moderate (ZIIIS2 & ZIIS1), and advanced (ZIIS2) ROP groups. With the different wave points of Raman spectra as the inputs, the outputs of our support vector machine showed that the area under the curves in the receiver operating characteristic (AUC) were 0.763 for the pair comparisons of the control with the mild groups, 0.821 between moderate and advanced groups (ZIIS2), while more than 90% in comparisons of the other four pairs: control vs. moderate (0.981), control vs. advanced (0.963), mild vs. moderate (0.936), and mild vs. advanced (0.953), respectively. Our study could advance principally the ROP diagnosis in two dimensions: the moderate ROPs have been classified remarkably from the mild ones, which leaves more time for the medical treatments, and the procedure of Raman spectrum with a machine learning model based on blood samples can be conveniently promoted to those hospitals lacking of the pediatric ophthalmologists with experience in reading retinal images. • A novel approach to classifying ROP with mild symptoms that require regular screening but not immediate medical intervention. • The moderate ROPs (ZIIIS2 & ZIIS1) and advanced ROPs (ZIIS2) have been distinguished remarkably from the mild ones (ZIIIS1). • Probably first demonstration of the feasibility of using machine learning to diagnose ROP based on plasma Raman spectrums. [ABSTRACT FROM AUTHOR]

Nrf2 gene encodes a transcription factor regulating the expression of antioxidant and detoxification genes. We test here whether Nrf2 plays a role for cardiac protection during ischemic injury in an effort to establish Nrf2 as a target for cardiac protection therapies. Cardiac ischemia induced by the left anterior descending (LAD) coronary artery ligation results in myocardial infarction (MI). Young mice surviving MI show minimal signs of heart failure. Mice lacking Nrf2 experience an accelerated progression to heart failure that occurs within 10 days following induction of MI. Nrf2 knockout (Nrf2 KO) mice have a survival rate similar to wild type (WT) mice at 24 h after MI, but a significantly higher mortality rate within 10 days after MI (50% vs 86%). Morphological examination revealed maladaptive remodeling, including cardiac hypertrophy and dilated left ventricle in Nrf2 KO mice, which were absent in WT mice. Measurements of cardiac function revealed increased left ventricular mass and decreases in cardiac output in Nrf2 KO mice. In addition, Nrf2 KO mice show biomarkers of heart failure, such as elevated levels of β-MHC, ANF, and BNP mRNA in the myocardium. These data support that Nrf2 plays an important role in protecting the myocardium from ischemic injury. Lack of Nrf2 leads to rapid development of heart failure. [ABSTRACT FROM AUTHOR]

Objective Seizure-related respiratory and cardiac dysfunctions were once thought to be the direct cause of sudden unexpected death in epilepsy (SUDEP), but both may be secondary to postictal cerebral inhibition. An important issue that has not been explored to date is the neural network basis of cerebral inhibition. Our aim was to investigate the features of neural networks in patients at high risk for SUDEP using a blood oxygen level-dependent (BOLD) resting-state functional connectivity (FC) approach. Subjects and methods Resting-state functional magnetic resonance imaging (Rs-fMRI) data were recorded from 13 patients at high risk for SUDEP and 12 patients at low risk for SUDEP. Thirteen cerebral regions that are closely related to cardiorespiratory activity were selected as regions of interest (ROIs). The ROI-wise resting-state FC analysis was compared between the two groups. Results Compared with patients at low risk for SUDEP, patients at high risk exhibited significant reductions in the resting-state FC between the pons and the right thalamus, the midbrain and the right thalamus, the bilateral anterior cingulate cortex (ACC) and the right thalamus, and the left thalamus and the right thalamus. Conclusions This investigation is the first to use neuroimaging methods in research on the mechanism of SUDEP and demonstrates the abnormally decreased resting-state FC in the ACC–thalamus–brainstem circuit in patients at high risk for SUDEP. These findings highlight the need to understand the fundamental neural network dysfunction in SUDEP, which may fill the missing link between seizure-related cardiorespiratory dysfunction and SUDEP, and provide a promising neuroimaging biomarker for risk prediction of SUDEP. [ABSTRACT FROM AUTHOR]

Abstract: Endothelial progenitor cells (EPCs) exhibit impaired function in the context of diabetes, and advanced glycation end products (AGEs), which accumulate in diabetes, may contribute to this. In the present study, we investigated the mechanism by which AGEs impair late EPC function. EPCs from human umbilical cord blood were isolated, and incubated with AGE-modified albumin (AGE-albumin) at different concentrations found physiologically in plasma. Apoptosis, migration, and tube formation assays were used to evaluate EPC function including capacity for vasculogenesis, and expression of the receptor for AGEs (RAGE), Akt, endothelial nitric oxide synthase (eNOS), and cycloxygenase-2 (COX-2) were determined. Anti-RAGE antibody was used to block RAGE function. AGE-albumin concentration-dependently enhanced apoptosis and depressed migration and tube formation, but did not affect proliferation, of late EPCs. High AGE-albumin increased RAGE mRNA and protein expression, and decreased Akt and COX-2 protein expression, whilst having no effect on eNOS mRNA or protein in these cells. These effects were inhibited by co-incubation with anti-RAGE antibody. These results suggest that RAGE mediates the AGE-induced impairment of late EPC function, through down-regulation of Akt and COX-2 in these cells. [Copyright &y& Elsevier]

Abstract: Chronic exposure to arsenic has been linked to tumorigenesis, cardiovascular disease, hypertension, atherosclerosis, and peripheral vascular disease; however, the molecular mechanisms underlying its pathological effects remain elusive. In this study, we investigated arsenic-induced alteration of focal adhesion protein complexes in normal, primary vascular smooth muscle cells. We demonstrate that exposure to environmentally relevant concentrations of arsenic (50 ppb As3+) can alter focal adhesion protein co-association leading to activation of downstream pathways. Co-associated proteins were identified and quantitated via co-immunoprecipitation, SDS-PAGE, and Western blot analysis followed by scanning densitometry. Activation of MAPK pathways in total cell lysates was evaluated using phosphor-specific antibodies. In our model, arsenic treatment caused a sustained increase in FAK–src association and activation, and induced the formation of unique signaling complexes (beginning after 3-hour As3+ exposure and continuing throughout the 12-hour time course studied). The effects of these alterations were manifested as chronic stimulation of downstream PAK, ERK and JNK pathways. Past studies have demonstrated that these pathways are involved in cellular survival, growth, proliferation, and migration in VSMCs. [Copyright &y& Elsevier]

Abstract: After an unilateral lesion of the corticospinal tract (CST) at the level of the medulla over-expression of Neurotrophin-3 (NT-3) in lumbar spinal cord motoneurons induced axonal sprouting of the intact CST in the acutely injured but not uninjured or chronically injured spinal cord in rats. This suggested that processes associated with immune-mediated wound healing may act with NT-3 to induce neuroplasticity. To test whether immune processes were involved we measured NT-3-induced axonal sprouting in immunosuppressed compared to immunocompetent rats. Rats were immunosuppressed with anti-leukocyte antibodies 1 day before receiving a CST lesion and then 2 weeks later NT-3 was over-expressed in the lumbar spinal motoneurons with an adenoviral vector carrying the NT-3 gene targeted to the motoneurons by retrograde transport. At 35 days post-lesion no axonal sprouting was measured in immunosuppressed rats whereas axonal sprouting was measured in the immunocompetent rats. We then tested whether re-evoking an immune response in chronically lesioned rats would induce neuroplasticity. Rats received CST lesions and then 4 months later were treated with systemic injections of lipopolysaccharide (LPS) 7 days before NT-3 was over-expressed in the lumbar spinal motoneurons. Axonal sprouting was observed in the LPS treated rats but not in control animals that were not treated with LPS. Further studies showed that lesioning the CST activated and LPS reactivated microglia and CD4+ T-cells in the acutely lesioned and chronically lesioned rats, respectively. However, immunosuppression only decreased the number of activated CD4+ T-cells suggesting they were responsible for the support of axonal growth. These observations demonstrate that processes associated with immune-mediated wound healing play a role in NT-3-induced neuroplasticity after injury. [Copyright &y& Elsevier]

Abstract: Midkine (MK) is a retinoic acid response cytokine, mostly expressed in embryonic tissues. Aberrant expression of MK was found in numerous cancers. In human, a truncated MK was expressed specifically in tumor/cancer tissues. Here we report the discovery of a novel truncated form of MK transiently expressed during normal mouse embryonic development. In addition, MK is concentrated at the interface between developing epithelium and mesenchyme as well as highly proliferating cells. Its expression, which is closely coordinated with angiogenesis and vasculogenesis, is spatiotemporally regulated with peaks in extensive organogenesis period and undifferentiated cells tailing off in maturing cells, implying its role in nascent blood vessel (endothelial) signaling of tissue differentiation and stem cell renewal/differentiation.. Cloning and sequencing analysis revealed that the embryonic truncated MK, in which the conserved domain is in-frame deleted, presumably producing a novel secreted small peptide, is different from the truncated form in human cancer tissues, whose deletion results in a frame-shift mutation. Our data suggest that MK may play a role in epithelium–mesenchyme interactions, blood vessel signaling, and the decision of proliferation vs differentiation. Detection of the transiently expressed truncated MK reveals its novel function in development and sheds light on its role in carcinogenesis. [Copyright &y& Elsevier]

[Display omitted] • Based on the binding pattern of the N -terminal region of CCR3 protein to CCL11, a series of cyclic peptides targeting the C C motif chemokine receptor 3 (CCR3) have been designed. • Optimized compound IB-2 may have a protective effect on photoreceptor cells. • Optimized compound IB-2 demonstrated good anti-angiogenic activity in vitro experiments. • In vivo experiments, Optimized compound IB-2 demonstrated promising therapeutic efficacy. The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting C C motif chemokine receptor 3 (CCR3). Based on the binding mode of the N -terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development. [ABSTRACT FROM AUTHOR]

This paper develops the virtual cylinder model (VCM) to simulate flows through vegetation canopies at low to medium high Reynolds numbers in wetlands. Using a combined Eulerian and Lagrangian approach, the VCM is capable of simulating the flow field around each vegetation stem (modeled as a cylinder) as well as a bulk of numerous stems in a fluid. Numerical results of flows through regularly and randomly arranged cylinders have been compared with direct numerical simulations. Good agreement has been achieved. This model maintains an excellent balance between accuracy and efficiency in modeling interactions between the fluid and vegetation stems. Simulation results demonstrate that this model is promising for investigating the hydrodynamics and vegetation resilience in wetlands that serve as a first line of defense against the sea level rise, storm impacts and coastal erosion. [ABSTRACT FROM AUTHOR]

In this study, sixteen evaluation indicators of explosion puffing Fuji apple chips from nine different origins in China were analyzed, and the most important evaluation indicators were obtained by analysis of variance (ANOVA), correlation analysis (CA), principal component analysis (PCA) and system cluster analysis (SCA). Results of ANOVA showed that quality of apple chips from different origins showed significant differences ( P < 0.05). The coefficient of variation (CV) values of sixteen evaluation indicators for apple chips from nine origins were 5.39 %–56.26%. Through CA results, some indicators were correlated to each other within a certain range, such as crude fat content and crispness. Five principle components were extracted through PCA with eigenvalue of over 1, and the cumulative contribution was achieved at 91.06%. Based on the above results, five characteristic indicators of apple chip quality were obtained by SCA. These were crude fiber content, crispness, titratable acid content, production rate and expansion ratio. [ABSTRACT FROM AUTHOR]

Abstract: Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. [Copyright &y& Elsevier]

Aging is the highest risk factor for cancer. Although oxidants are thought to contribute to both aging and cancer, the interplay between oxidative stress, aging, and cancer has not been well studied. Human diploid fibroblasts (HDFs) undergo premature senescence in response to sublethal doses of H2O2. To test the hypothesis that senescent or senescent-like HDFs function as a tumor promoter, we have employed an in vitro skin tumor promotion model, in which colony formation is measured using initiated mouse keratinocyte 308 cells seeded at clonal density. 308 cells form colonies when co-cultured with normal HDFs only in the presence of the tumor promoter phorbol 12-myristate 13-acetate (TPA), which induces an average of 5.75 colonies. When co-cultured with H2O2-treated HDFs, 308 cells form an average of 30.3 colonies. To understand the mechanism behind this phenomenon, we tested whether conditioned medium of HDFs, HDF extracellular matrix (ECM), density of HDFs, or the contact between keratinocytes and HDFs plays a role in 308 cell colony formation. The conditioned medium from prematurely senescent cells resulted in an average of eightfold more 308 cell colonies formed than the conditioned medium from normal HDFs, and the growth-promoting effect of the conditioned medium was trypsin sensitive. The ECM alone was not able to induce 308 cell colony formation. Increasing the density of normal HDFs or contact with normal HDFs but not senescent-like HDFs was inhibitory to the growth of 308 cells. Measurement of Connexin 43 indicated a decreased expression of the protein, which suggests an impaired gap junction communication in senescent-like HDFs. We conclude that H2O2-treated fibroblasts not only lose contact inhibition of the growth of initiated keratinocytes perhaps related to reduced gap junction communication but also increase production of secreted protein factors to enhance the growth of 308 keratinocytes. [Copyright &y& Elsevier]

Glioma is the most lethal nervous system cancer. Recent studies have made great efforts to study the occurrence and development of glioma, but the molecular mechanisms are still unclear. This study was designed to reveal the molecular mechanisms of glioma based on protein-protein interaction network combined with machine learning methods. Key differentially expressed genes (DEGs) were screened and selected by using the protein-protein interaction (PPI) networks. As a result, 19 genes between grade I and grade II, 21 genes between grade II and grade III, and 20 genes between grade III and grade IV. Then, five machine learning methods were employed to predict the gliomas stages based on the selected key genes. After comparison, Complement Naive Bayes classifier was employed to build the prediction model for grade II-III with accuracy 72.8%. And Random forest was employed to build the prediction model for grade I-II and grade III-VI with accuracy 97.1% and 83.2%, respectively. Finally, the selected genes were analyzed by PPI networks, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the results improve our understanding of the biological functions of select DEGs involved in glioma growth. We expect that the key genes expressed have a guiding significance for the occurrence of gliomas or, at the very least, that they are useful for tumor researchers. Machine learning combined with PPI networks, GO and KEGG analyses of selected DEGs improve our understanding of the biological functions involved in glioma growth. • Glioma is the most lethal nervous system cancer • Its molecular mechanisms are still unclear • This study has revealed the molecular mechanisms of glioma [ABSTRACT FROM AUTHOR]

High-throughput sequencing for transcriptome profiling is an increasingly accessible and important tool for biological research. However, accurate profiling of small cell populations remains challenging due to issues with gene detection sensitivity and experimental complexity. Here we describe a streamlined RNAseq protocol (EASY RNAseq) for sensitive transcriptome assessment starting from low amount of input materials. EASY RNAseq is technically robust enough for sequencing small pools of cells, recovering information on larger amounts of genes and with a more even expression distribution pattern than other commonly used methods. Application of EASY RNAseq to single-human embryos at the 8-cell stage led to detection of 70% of currently annotated protein-coding genes. This workflow may thus serve as a useful tool for sensitive interrogation of rare cell populations. Unlabelled Image • EASY RNAseq allows for rapid library construction for next-generation sequencing. • EASY RNAseq can recover rare transcripts from low amounts of sample input. • EASY RNAseq can obtain transcriptome information of small amounts of cells. [ABSTRACT FROM AUTHOR]

Objective Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). Methods Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. Result The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. Conclusion Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function. [ABSTRACT FROM AUTHOR]

The Auxin/indole-3-acetic acid ( Aux/IAA ) genes encode short-lived nuclear proteins that are known to be involved in the primary cellular responses to auxin. To date, systematic analysis of the Aux/IAA genes in potato ( Solanum tuberosum ) has not been conducted. In this study, a total of 26 potato Aux/IAA genes were identified (designated from StIAA1 to StIAA26 ), and the distribution of four conserved domains shared by the StIAAs were analyzed based on multiple sequence alignment and a motif-based sequence analysis. A phylogenetic analysis of the Aux/IAA gene families of potato and Arabidopsis was also conducted. In order to assess the roles of StIAA genes in tuber development, the results of RNA-seq studies were reformatted to analyze the expression patterns of StIAA genes, and then verified by quantitative real-time PCR. A large number of StIAA genes (12 genes) were highly expressed in stolon organs and in during the tuber initiation and expansion developmental stages, and most of these genes were responsive to indoleacetic acid treatment. Our results suggested that StIAA genes were involved in the process of tuber development and provided insights into functional roles of potato Aux/IAA genes. [ABSTRACT FROM AUTHOR]

Nrf2 encodes a transcription factor best known for regulating the expression of antioxidant and detoxification genes. Recent evidence suggested that Nrf2 mediates metabolic reprogramming in cancer cells. However, the role of Nrf2 in the biochemical metabolism of cardiac cells has not been studied. Using LC-MS/MS-based metabolomics, we addressed whether knocking out the Nrf2 gene in AC16 human cardiomyocytes affects metabolic reprogramming by oxidative stress. Profiling the basal level metabolites showed an elevated pentose phosphate pathway and increased levels of sugar alcohols, sorbitol, L-arabitol, xylitol and xylonic acid, in Nrf2 KO cells. With sublethal levels of oxidative stress, depletion of NAD, an increase of GDP and elevation of sugar alcohols, sorbitol and dulcitol, were detected in parent wild type (WT) cells. Knocking out Nrf2 did not affect these changes. Biochemical assays confirmed depletion of NAD in WT and Nrf2 KO cells due to H 2 O 2 treatment. These data support that although Nrf2 deficiency caused baseline activation of the pentose phosphate pathway and sugar alcohol synthesis, a brief exposure to none-lethal doses of H 2 O 2 caused NAD depletion in an Nrf2 independent manner. Loss of NAD may contribute to oxidative stress associated cell degeneration as observed with aging, diabetes and heart failure. • Nrf2 effect on metabolic reprogramming by oxidants was determined via metabolomics. • Oxidant causes NAD decrease but increased sugar alcohols in AC16 cardiomyocytes. • Nrf2 knockout did not affect these metabolic reprogramming by oxidative stress. • Nrf2 knockout caused a baseline increase of pentose phosphate pathway. [ABSTRACT FROM AUTHOR]

Abstract: One of the major challenges in developing novel therapeutics for human epileptic disorders derives from the limitation of knowledge of the processes by which epilepsy is generated (epileptogenesis). Furthermore, the inability to obtain human samples at the early stage of epilepsy hinders studies designed to further understand epileptogenesis. Thus, an effective animal model is critical for studies investigating this process. The purpose of this study was to establish a new primate kindling model of temporal lobe epilepsy (TLE) as an animal model of epileptogenesis. Here, repeated injections of Coriaria lactone (CL) at a subthreshold dose elicited partial seizures that culminated in secondarily generalized tonic–clonic seizures. The sequence of events and features of the behaviors observed in this model simulated those observed in human TLE. Electroencephalogram monitoring revealed the temporal lobe origins of the epileptiform potentials, which were consistent with the behavioral changes observed. A total of 7 rhesus monkeys (78%) were kindled with a median of 48 (41 to 60) CL injections. Both the seizure-induction and mortality rates were dose-dependent. A CL injection at 1.50mg/kg showed the lowest animal mortality rate (0%) and the highest seizure-induction rate (100%). Extensive kindling by CL injections with a median of 97 injections (overkindling) subsequently resulted in the recurrence of spontaneous seizures in rhesus monkeys with frequency patterns that were similar to those observed in human TLE. In addition, rhesus monkeys subjected to large numbers of kindling stimuli displayed mitochondrial damage and astrocyte activation in a pattern that was similar to the neuropathological changes characteristic of human TLE. Thus, a kindling TLE model in rhesus monkeys representing a primate animal model of epileptogenesis was established for the first time using repeated intramuscular injections of Coriaria lactone. This model was easily and efficiently performed and resulted in behavioral, electrographical, and anatomical characteristics of human TLE. Thus, this model might be used in future investigations of the mechanisms involved in the epileptogenesis of TLE and in the development of new antiepileptic drugs. [Copyright &y& Elsevier]

Abstract: Salt and alkali stress are two of the main environmental factors limiting crop production. Recent discoveries show that the JAZ family encodes plant-specific genes involved in jasmonate signaling. However, there is only limited information about this gene family in abiotic stress response, and in wild soybean (Glycine soja), which is a species noted for its tolerance to alkali and salinity. Here, we isolated and characterized a novel JAZ family gene, GsJAZ2, from G. soja. Transcript abundance of GsJAZ2 increased following exposure to salt, alkali, cold and drought. Over-expression of GsJAZ2 in Arabidopsis resulted in enhanced plant tolerance to salt and alkali stress. The expression levels of some alkali stress response and stress-inducible marker genes were significantly higher in the GsJAZ2 overexpression lines as compared to wild-type plants. Subcellular localization studies using a GFP fusion protein showed that GsJAZ2 was localized to the nucleus. These results suggest that the newly isolated wild soybean GsJAZ2 is a positive regulator of plant salt and alkali stress tolerance. [Copyright &y& Elsevier]

Abstract: Doxorubicin (Dox) is an antineoplastic agent that can cause cardiomyopathy in humans and experimental animals. As an inducer of reactive oxygen species and a DNA damaging agent, Dox causes elevated expression of p21WAF1/Cip1/Sdi1 (p21) gene. Elevated levels of p21 mRNA and p21 protein have been detected in the myocardium of mice following Dox treatment. With chronic treatment of Dox, wild type (WT) animals develop cardiomyopathy evidenced by elongated nuclei, mitochondrial swelling, myofilamental disarray, reduced cardiac output, reduced ejection fraction, reduced left ventricular contractility, and elevated expression of ANF gene. In contrast, p21 knockout (p21KO) mice did not show significant changes in the same parameters in response to Dox treatment. In an effort to understand the mechanism of the resistance against Dox induced cardiomyopathy, we measured levels of antioxidant enzymes and found that p21KO mice did not contain elevated basal or inducible levels of glutathione peroxidase and catalase. Measurements of 6 circulating cytokines indicated elevation of IL-6, IL-12, IFNγ and TNFα in Dox treated WT mice but not p21KO mice. Dox induced elevation of IL-6 mRNA was detected in the myocardium of WT mice but not p21KO mice. While the mechanism of the resistance against Dox induced cardiomyopathy remains unclear, lack of inflammatory response may contribute to the observed cardiac protection in p21KO mice. [Copyright &y& Elsevier]

Abstract: Decreased levels of circulating endothelial progenitor cells (EPCs) predict increased risk of cardiovascular events in diabetic patients. Insulin treatment exerts important cardiovascular protection. Whether and how insulin participates in the EPC regulation of postnatal neovascularization are currently unclear. We employed a mouse hindlimb ischemia model to study EPC mobilization in non-diabetic and streptozotocin-induced diabetic mice. Insulin was administered to diabetic animals postoperatively. To determine the role of EPCs contributing to postnatal vasculogenesis, we used bone marrow-transplanted mice whose bone marrow cells selectively expressed enhanced green fluorescent protein (EGFP). Insulin treatment improved EPC mobilization into peripheral blood, accelerated transcutaneous oxygen pressure restoration and increased capillary density in the ischemic limb associated with partial incorporation of EGFP-positive cells into the capillaries. Insulin treatment restored ischemia-induced release of stromal-derived growth factor 1α and vascular endothelial growth factor (VEGF), and consequently enhanced the activity of Akt and endothelial nitric oxide synthase (eNOS) as well as matrix metalloproteinase-9 in bone marrow. Insulin also augmented tissue-level activation of VEGF/Akt/eNOS pathway. However, all such effects of insulin were completely blocked by combined treatment with a NOS inhibitor. Our data suggested that insulin treatment improved ischemia-induced EPC mobilization and contributed to compensatory neovascularization in diabetic mice through a VEGF/eNOS-related pathway. [Copyright &y& Elsevier]

Abstract: Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca2+ concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study was to establish the prevalence rate of convulsive epilepsy and the treatment gap in some rural areas of Tibet Autonomous Region in China, to evaluate the quality of life (QOL) of patients with epilepsy and identify factors contributing to their QOL. Methods: A door-to-door epidemiological survey using randomized cluster sampling was conducted in a rural population in Tibet. A screening questionnaire for convulsive epilepsy was used. Clinical and sociodemographic data were collected from patients confirmed as having convulsive epilepsy. QOL was measured with the Quality of Life in Epilepsy inventory (QOLIE-31). Factors associated with QOLIE-31 total and subcomponent scores were analyzed by multiple regression analysis. Results: A total of 14,822 people were screened. Of these, 37 were confirmed to have convulsive epilepsy, which was active in 35. Lifetime prevalence was estimated to be 2.5 per 1000 in this population. Nearly 60% of patients received traditional Tibetan treatment; 97% of the patients with active epilepsy did not receive reasonable antiepileptic therapy in the week before the survey (treatment gap). The mean QOLIE-31 total score was 42.2 (SD 17.6), with the lowest subcomponent score 22.6 (SD 20.3) for Seizure Worry and the highest 85.8 (SD 18.6) for Medication Effects. High seizure frequency, low economic status, advanced age, late seizure onset, and high education level significantly correlated with low QOLIE-31 total and/or subcomponent scores. Conclusions: The prevalence rate for epilepsy was relatively lower than reported for other rural regions; however, the large treatment gap and poor QOL indicated the pressing needs for medical, financial, and social support in this population. [Copyright &y& Elsevier]

Abstract: Mild or low doses of oxidants are known to prime cells towards resistance against further damage. In cardiomyocytes, we found that pretreatment with 100 μM H2O2 prevents the cells from apoptosis induced by doxorubicin (Dox). Affymetrix microarray analyses of 28,000 genes reveal that H2O2 treated cells reduced expression of genes encoding cytochrome c, mitochondrial complex I, III, IV and V and several contractile proteins. Elevated expression of antioxidant and detoxification genes appears as a dominant feature of the gene expression profile of H2O2 treated cells. Most of the genes in this category contain an Antioxidant Response Element (ARE) in their promoters. Measurements of ARE promoter–reporter gene activity indicate a dose- and time-dependent activation of the ARE by H2O2. Since the Nrf2 transcription factor regulates ARE-mediated gene expression, we overexpressed Nrf2 to test whether activation of Nrf2 is sufficient to induce cytoprotection. High levels of Nrf2 expression were achieved via adenovirus mediated gene delivery. Transduced Nrf2 was present in the nuclei and caused an increase in the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1), a representative downstream target of Nrf2. Unlike H2O2 pretreated cells, the cells expressing high levels of Nrf2 were not resistant to Dox-induced apoptosis. Therefore, the cytoprotective effect of H2O2 pretreatment is not reliant upon Nrf2 activation alone as measured by resistance against Dox-induced apoptosis. [Copyright &y& Elsevier]

A cellulose hydrolytic enzyme was isolated from the stomach juice of Ampullaria crossean, a kind of herbivorous mollusca. The enzyme was purified 45.3-fold to homogenety by ammonium sulfate precipitation, DEAE-Sephadex A-50 column, Bio-gel P-100 gel filtration column, and phenyl-Sepharose CL-4B column chromatography. The enzyme was designated as cellulase EGX. The purified enzyme is a multi-functional enzyme with the activities of exo-β-1,4-glucanase (14.84 U/mg for p-nitrophenyl β-d-cellobioside), endo-β-1,4-glucanase (40.3 U/mg for carboxymethyl cellulose), and endo-β-1,4-xylanase (196 U/mg for soluble xylan from birchwood). The monovalent anions such as F−, Cl−, Br−, I−, and NO3− are essential for its exo-β-1,4-glucanase activity but have no effect on the activity for xylan, while I− higher than 5 mM would inhibit the exo-β-1,4-glucanase activity. The monovalent anions Cl− and Br− activate its endo-β-1,4-glucanase activity. Binding of Cl− enhances the thermostability of EGX, but does not affect its fluorescence emission spectrum. The molecular mass of EGX is 41.5 kDa, as determined by SDS–PAGE. The pI value is about pH 7.35. The xylan hydrolytic activity of EGX reaches to the maximum between pH 4.8 and 6.0 and the pNPC hydrolytic activity reaches the maximum between pH 4.8 and 5.6, while that for CMC hydrolytic activity is between pH 4.4 and 4.8. Preliminary results showed that the enzyme was secreted by the mollusca itself. [Copyright &y& Elsevier]

• Tissue-resident macrophages exhibit distinct tissue-specific and niche-specific functions in homeostatic maintenance. • Inflammaging of tissue-resident macrophages contribute to homeostasis dysregulation. • Tissue-resident macrophages are involved in the maintenance of inflammaging and age-related diseases. Organs and tissues contain a large number of tissue-resident macrophages (MΦ-Ts), which are essential for regulating homeostasis and ensuring a rapid response to injury. However, the environmental signals shaping MΦ-Ts phenotypes and the contribution of MΦ-Ts to pathological processes are just starting to be identified. MΦ-Ts isolated from aged animals or patients show alterations in morphology and distribution, defects in phagocytosis and autophagy, and loss of tissue-repair capacity. These variations are closely associated with age-associated disorders, such as inflammaging, which is characterized by cell senescence and a senescence-associated secretory phenotype (SASP) and is frequently observed in patients afflicted with chronic diseases. It seems that the role of these resident populations cannot be avoided in the treatment of aging-related diseases. This review will describe the mechanism by which MΦ-Ts support immune homeostasis and will then discuss how MΦ-Ts facilitate inflammaging and age-related diseases, which will be helpful in the development of new interventions and treatments for chronic diseases of the elderly. [ABSTRACT FROM AUTHOR]