By means of field sampling and laboratory analysis, the content distribution characteristics of Cd, Cr, Cu, Ni, Pb and Zn in agricultural region soils of Huaihe basin in Anhui province were analyzed. Assessment of heavy metal pollutions was conducted using enrichment factor, geoaccumulation index and potential ecological risk index. The results showed that the average mass fraction of Cd and Cu was 0.113 5 and 22.09 mg x kg(-1) respectively in the study area soil, which were above the background values 0.097 and 20.4 mg x kg(-1) in Anhui Province. The average mass fraction of other four heavy metals did not exceed the average values of Anhui Province. The results of the evaluations from geoaccumulation index and ecological risk assessment discovered that Cd is the strongest pollution metal among six heavy metals in the study area soil. For some samples of the study soil, Cd was slight risk for the ecosystem. The ecosystem risks caused by the other five heavy metals were not obviously for the sampling points. The entire study area soils were mid integrated potential ecological risk.
Four hundred sixty-two nalidixic acid- and/or ciprofloxacin-resistant Salmonella isolates were examined for presence of quinolone-resistance mechanisms. A total of 339 amino acid substitutions were identified in GyrA (204) and ParC (135). Ser83Phe/Asp87Gly (29.4%) were most commonly detected in GyrA in 136 isolates, and to a lesser extent of Asp87Asn (22.8%), Asp87Gly (19.1%), Ser83Phe/Asp87Asn (19.1%), and Ser83Tyr (5.1%). Ser80Arg (97.0%) was detected in ParC in 132 isolates. Simultaneous mutations in GyrA and ParC (n=109) were commonly detected to be Ser83Phe/Asp87Gly(GyrA)-Ser80Arg(ParC) (35.8%), Asp87Asn(GyrA)-Ser80Arg(ParC) (22.9%), and Ser83Phe/Asp87Asn(GyrA)-Ser80Arg(ParC) (21.1%). qnrA, qnrB, qnrS, aac(6')-Ib, qepA, and oqxAB were detected in 52 (11.3%), 64 (13.9%), 11(2.4%), 107 (23.2%), 6 (1.3%), and 194 (42.0%) of 462 isolates, respectively. Isolates carried more qnr, aac(6')-Ib, qepA, and oqxAB genes, and amino acid substitution in GyrA and ParC was more resistant to nalidixic acid and fluoroquinolones.
The p53 protein is involved in many biological functions in cancer, such as cell cycle arrest, DNA repair, apoptosis, senescence, DNA metabolism, angiogenesis, and cellular differentiation. However, the association between p53 expression and clinicopathological findings or prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. We designed a large-scale study of 830 operable ESCC patients with a long follow-up to investigate the relationship between p53 expression and the clinicopathological characteristics and prognosis of patients. Immunohistochemistry was used to detect p53 protein expression. When the patients were divided into two groups, a positive expression group and a negative expression group, p53-positive expression positively correlated with a poorer differentiation level (P = 0.044). The overexpression of p53 was associated with a more advanced clinical stage (P = 0.015). A total of 775 patients were available for survival analysis. The median OS of 160 patients who had p53-positive expression and 486 patients who had p53-negative expression were 58.8 and 46.3 months, respectively (P = 0.021); the median PFS of the two groups were 39.6 and 27.5 months, respectively (P = 0.015). Lymph node metastasis, gender, differentiation, depth of invasion, and p53 protein expression were proven to have an influence on both OS and PFS in a univariate analysis. In the multivariate analysis, p53-positive expression maintained its independent prognostic impact on OS (P = 0.048) and PFS (P = 0.039), as did lymph node metastasis, differentiation, and depth of invasion. We identified that p53 protein-positive expression can serve as an independent, unfavorable prognosis biomarker in ESCC.
Morphological observation of arbuscular mycorrhizal fungi (AMF) species in rhizospheric soil could not accurately reflect the actual AMF colonizing status in roots, while molecular identification of indigenous AMF colonizing citrus rootstocks at present was rare in China. In our study, community of AMF colonizing trifoliate orange (Poncirus trifoliata L. Raf.) and red tangerine (Citrus reticulata Blanco) were analyzed based on small subunit of ribosomal DNA genes. Morphological observation showed that arbuscular mycorrhizal (AM) colonization, spore density, and hyphal length did not differ significantly between two rootstocks. Phylogenetic analysis showed that 173 screened AMF sequences clustered in at least 10 discrete groups (GLO1~GLO10), all belonging to the genus of Glomus Sensu Lato. Among them, GLO1 clade (clustering with uncultured Glomus) accounting for 54.43% clones was the most common in trifoliate orange roots, while GLO6 clade (clustering with Glomus intraradices) accounting for 35.00% clones was the most common in red tangerine roots. Although, Shannon-Wiener indices exhibited no notable differences between both rootstocks, relative proportions of observed clades analysis revealed that composition of AMF communities colonizing two rootstocks varied severely. The results indicated that native AMF species in citrus rhizosphere had diverse colonization potential between two different rootstocks in the present orchards.
Microglial activation has been recognized as being vital in the pathogenesis of several neurodegenerative disorders. Therefore, the identification of therapeutic drugs to prevent microglial activation and thus protect against inflammation?mediated neuronal injury, is required. In the present study, dextromethorphan (DM), a compound widely used in antitussive remedies that has been demonstrated to possess neuroprotective effects, was shown to reduce proinflammatory mediator production in lipopolysaccharide (LPS)?stimulated BV2 mouse microglial cells. Western blot analysis revealed that DM markedly suppressed the activation of nuclear factor??B (NF?B), caspase?3 signaling and the expression of another inflammation?inducing factor, heat shock protein 60 (HSP60) and heat shock factor?1, induced by LPS in BV2 cells. Results from ELISA assay demonstrated that DM reduced the release of HSP60, nitric oxide (NO), inducible NO synthase, tumor necrosis factor??, interleukin (IL)?1? and IL?6 induced by LPS in BV2 microglia. These results were confirmed by immunofluorescence, suggesting that DM may exert a neuroprotective and anti?inflammatory effect by inhibiting microglial activation through the HSP60?NF?B signaling pathway. Therefore, DM may offer substantial therapeutic benefits in the treatment of neurodegenerative diseases that are accompanied by microglial activation.
The neural and cognitive mechanisms by which primed constructs can impact on social behavior are poorly understood. In the present study, we used functional magnetic resonance imaging (fMRI) to explore how scrambled sentence priming can impact on mimicry behavior. Sentences involving pro/antisocial events from a first/third-person point of view were presented in short blocks, followed by a reaction-time assessment of mimicry. Behavioral results showed that both prosociality and viewpoint impact on mimicry, and fMRI analysis showed this effect is implemented by anterior medial prefrontal cortex (amPFC). We suggest that social primes may subtly modulate processing in amPFC in a manner linked to the later behavior, and that this same region also implements the top-down control of mimicry responses. This priming may be linked to processing of self-schemas in amPFC. Our findings demonstrate how social priming can be studied with fMRI, and have important implications for our understanding of the underlying mechanisms of prime-to-behavior effects as well as for current theories in social psychology.
The one of the advantages about Laser Induced Breakdown Spectroscopy (LIBS) is multielement detection at the same time. In order to obtain the optimum signal in the multi-element measurements of water with LIBS, the present paper firstly models the numerical relationship between the signal-to-background ratio of characteristic spectral lines and the delay time and gate width time with BP neural network, using DM design experiment data as the checking sample to ensure the generalization ability of the BP neural network model. Based on the above model, genetic algorithm is used to optimize measurement parameters and the fitness function phi is defined. When the optimum delay time and gate width time is (15.5 micros, 21.5 micros), the minimum value of psi is 0.102 4. The optimization results of genetic algorithm are further confirmed with experimental results. So the method of parameters optimization overall improves S/B of multi-element measurements in water with LBS, and provides the reference for parameter optimization of other experiments.
The first attempt of constructing pH responsive supramolecular prodrug micelles based on cucurbituril is reported. The obtained prodrug micelles are found to be able to inhibit proliferation of cancer cells. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.
Nicrophorus vespilloides eggs are deposited into the soil in close proximity to the decomposing vertebrate carcasses that these insects use as an obligate resource to rear their offspring. Eggs in this environment potentially face significant risks from the bacteria that proliferate in the grave-soil environment following nutrient influx from the decomposing carcass. Our aims in this paper are twofold: first, to examine the fitness effects of grave-soil bacteria to eggs, and second, to quantify egg immunocompetence as a defence against these bacteria.
Acute myeloid leukemia (AML) often relapses following chemotherapy-induced remission and is generally chemo-resistant. Given the potential role for cancer stem cells in relapse, targeting of the leukemia-initiating cell (LIC) in AML may provide improved outcome following remission induction. However, due to overlap in their self-renewal program with normal hematopoietic stem cells (HSCs), therapeutic targeting of the LIC may have an adverse effect on long-term hematopoietic recovery. Here we used a mouse model of relapsed AML to explore whether the hypoxia-inducible factor (HIF)1? inhibitor echinomycin can be used to treat relapsed AML without affecting host HSCs. We show that echinomycin cured 40% to 60% of mice transplanted with relapsed AML. Bone marrow cells from the cured mice displayed normal composition of HSCs and their progenitors and were as competent as those isolated from nonleukemic mice in competitive repopulation assays. Importantly, in mice with complete remission, echinomycin appeared to completely eliminate LICs because no leukemia could be propagated in vivo following serial transplantation. Taken together, our data demonstrate that in a mouse model of relapsed AML, low-dose echinomycin selectively targets LICs and spares normal hematopoiesis.
Bronchiectasis is a chronic lung disorder and a number of bacterial pathogens are involved. However, 30%-40% of sputum and purulent samples in good quality failed to grow any pathogenic bacteria, making it difficult to confirm the pathogen. In this study, we collected bronchoalveolar lavage fluid from a bronchiectasis patient undergoing acute exacerbation, and sent for 16S rDNA pyrosequencing by a 454 GS Junior machine. Metagenomic analysis showed the composition of bacterial community in sample was complex. More than a half of reads (51.3%) were from Pseudomonas aeruginosa. This result was corresponding with the culture result but came out 2 d earlier, which is meaningful for early diagnosis and treatment. The detection with 16S rDNA pyrosequencing technology is more sensitive and rapid than routine culture, and can detect the co-infection or symbiosis in airway, giving us a novel and convenient approach to perform rapid diagnosis.
Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL), affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484) and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.
Helicobacter pylori (H. pylori) have been considered as a risk factor for many cancers. We conducted this meta-analysis to clarify the association between H. pylori infection and the risk of pancreatic cancer.
Danon disease is an Xlinked dominant lysosomal glycogen storage disorder characterized by cardiomyopathy, skeletal myopathy, and mental retardation. This study described two Chinese cases of Danon disease in order to broaden the phenotypic and genetic spectrum.
MicroRNAs (miRNAs) are an abundant group of small non-coding RNAs that have been implicated in tumorigenesis. They regulate expression of target genes by complementary base pairing. The purposes of this study were to delineate miR-106b expression in medulloblastoma (MB) and to explore its functional contributions to MB pathogenesis.
Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed.
Heat shock protein (HSP)60 is primarily a mitochondrial protein. Previous experiments have found that changes in the location of intracellular HSP60 have been associated with apoptosis. Extracellular HSP60 mediates apoptosis via its ligand, Toll?like receptor (TLR)-4. TLR-4 is an important factor expressed on microglia, with a central role in generating neuroimmune responses in the pathogenesis of neurodegenerative disorders. Naloxone is a highly effective nonselective opioid receptor antagonist, and has been reported to be pharmacologically beneficial for the treatment of brain diseases through inhibiting microglia activation. However, the mechanisms underlying these beneficial effects of naloxone remain poorly understood. The present study aimed to investigate the role of HSP60 in the neuroprotective effects of naloxone on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells and the possible signaling pathways involved. The results demonstrated that naloxone significantly inhibited the expression and release of HSP60 in BV2 cells. The expression levels of heat shock factor (HSF)-1 were upregulated in LPS?activated BV2 cells, which indicated that the increased expression of HSP60 was driven by HSF-1 activation. However, increased HSF?1 levels may be downregulated by naloxone. The levels of TLR?4 were elevated in activated BV2 cells, and then inhibited by naloxone. Activation of TLR?4 is characterized by activation of nuclear factor-?B (NF-?B) followed by the production of various proinflammatory and neurotoxic factors. Data from the present study demonstrated that naloxone reduced the expression levels of NF-?B and its upstream protein caspase?3, and reduced the LPS-induced production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor ?, interleukin-1? and interleukin-6 in BV2 microglia. In light of this data, it was concluded that naloxone may exert its neuroprotective and anti?inflammatory effects by inhibiting microglia activation through a HSP60?TLR?4?NF??B signaling pathway.
The purpose of this study was to explore new tumor suppressor microRNA in bladder cancer and to conduct functional analysis of its suppressive role. To investigate the expression of miR-29c, qRT-PCR was used in 30 pairs of bladder cancer tissues and normal tissues (adjacent bladder tissue samples). The expression of miR-29c was down regulated in bladder cancer tissues compared with normal tissues. Also, the low-level expression of miR-29c was associated with tumor stage (P = 0.002), and ectopic over-expression of miR-29c in T24 cells can significantly inhibit cell proliferation, decrease motility, suppress the G1/S cell cycle transition and induce apoptosis. Furthermore, it could cause a decrease in AKT and GSK-3? phosphorylation. While LY294002 reduced the protein level of pAKT, the over-expression of miR-29c can further decrease its level in T24 cells pretreated with LY294002. Our study also indicated that the proliferation inhibition of T24 may take place via AKT-GSK3? pathway. Thus, miR-29c could be an active player in disease state of bladder cancer and it may be a promising tumor suppressor in bladder cancer.
Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity.
Cell reprogramming is a process involved in changing epigenetic landscapes, including histone modification, DNA methylation, and expression of non-coding RNAs; and reprogramming finally leads to changes in gene expression profile and cell fate. A great challenge to this field is to overcome epigenetic suppression exerted by highly differentiated cells of those key regions that are critical for establishment and maintenance of final cell types or induced pluripotent stem cells (iPSCs). As a new class of small non-coding RNAs, piwi-interacting RNAs (piRNAs) have been shown to play important roles in transposon silencing, transcriptional/post-transcriptional regulation, and epigenetic modifications. In this review, we discuss recent advances in which piRNAs were proposed or shown to be barriers to reprogramming suppression through epigenetic silencing, and it may be necessary to overcome this piRNA-derived barrier to achieve final cellular status during reprogramming. Therefore, gaining deeper insights into the mechanism(s) by which piRNAs mediate epigenetic regulation of gene expression, genome stability and chromatin status may offer a new avenue for efficient reprogramming of somatic cells toward a pluripotent state.
We report a case of a 40-year-old woman who developed generalized muscle weakness over a period of 2months. Physical examination revealed palpable masses in her arms and hands. Serum creatine kinase levels were elevated. Electromyography showed myopathic changes and 3Hz repetitive nerve stimulation revealed a decremental pattern on repetitive nerve stimulation. Muscle MRI demonstrated increased signal intensity in the biceps brachii on T1-weighted images. Chest CT scan showed a mediastinal mass suggestive of thymoma. Muscle biopsy revealed giant cell polymyositis. The patient was treated with cholinesterase inhibitors and corticosteroids with improvement of strength, and subsequently underwent thymectomy followed by radiotherapy.
Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2) has been indicated to have a critical role in various tumors. In the study, we aimed to evaluate the LASS2 expression level in prognostic significance and compare it with commonly used biomarkers: Ki-67, p53 and progesterone receptor (PR) for patients with meningiomas. Firstly, 50 fresh tissues and 143 paraffin-embedded meningiomas samples were analyzed for LASS2 expression by quantitative PCR and immunohistochemistry (IHC), respectively. Subsequently, LASS2 immunostaining was evaluated for its clinical significance. Furthermore, Correlations of LASS2 expression with common biomarkers were assessed. Both PCR and IHC results showed LASS2 was downregulated in high-grade meningiomas in comparison with that of grade I or normal brain (all P < 0.01). IHC results demonstrated LASS2 intensity distribution (ID) score was significantly correlated with tumor size, brain invasion, tumor recurrence and clinical course (all P < 0.01), whereas no correlation of LASS2 ID score with sex or Simpson grade. Moreover, lower LASS2 ID score was strikingly associated with shorter overall and progression-free survival (P < 0.01). Pearson's analysis revealed the ID score was significantly reversely associated with Ki-67 and p53 but not with PR. More importantly,multivariate analyses revealed that LASS2 was an independent prognostic factor (P < 0.05). To our knowledge, it is the first time to investigate the expression of LASS2 and identify it as a potential biomarker for prognosis in meningiomas.
HepaCAM is suppressed in a variety of human cancers, and involved in cell adhesion, growth, migration, invasion, and survival. However, the expression and function of HepaCAM in prostate cancer are still unknown.
The technique of dual modulation Faraday rotation spectroscopy (DM-FRS) has been applied to achieve technical-noise-limited detection of HO2 at the exit of an atmospheric pressure flow reactor. This was implemented by combining direct current modulation at 51 kHz of an external cavity quantum cascade laser system with 610 Hz modulation of the magnetic field generated by a Helmholtz coil. The DM-FRS measurement had a 1.5 times better signal-to-noise ratio than a conventional FRS measurement acquired under identical flow reactor conditions. High harmonic detection of the FRS signal also eliminated the substantial offset associated with electromagnetic interference pickup from the Helmholtz coils that is observed in the conventional FRS spectrum. A noise equivalent angle of 8.9×10(-9)??rad?Hz(-1/2) was measured for the DM-FRS measurement, corresponding to a 3? detection limit for HO2 of 0.35??ppmv?Hz(-1/2).
A common single-nucleotide polymorphism identified in the 5'-untranslated region of the leptin gene (LEP -2548 G/A polymorphism) may be associated with obesity, but the existing research findings are inconsistent, so we conducted this meta-analysis.
The purpose of the present study was to investigate the effects of high ambient temperature on the neuropeptide Y (NPY) mRNA level in the hypothalamus, the plasma concentration of corticotropin-releasing hormone (CRH), cortisol (Cor), heat-shock protein 70 (HSP70) and epinephrine (EPI), and the intervention of lycium barbarum polysaccharides (LBPs) in rats. Compared to the control (CN) group, the plasma levels of CRH, Cor, HSP70 and EPI were markedly increased, and the level of NPY mRNA was downregulated in the high ambient temperature (HT) group. By contrast, rats in the HT + LBP (HTL) group had: i) a significantly enhanced expression of HSP70 compared to the HT and CN groups; ii) clearly increased plasma levels of CRH, Cor and EPI compared to the CN group; and iii) a markedly upregulated expression of NPY mRNA compared to the HT group. Thus, the results showed that high-temperature environments may damage the body, and LBPs have a potentially protective function by increasing the expression of HSP70 and NPY.
A novel amphiphilic ABA-type triblock copolymer poly(ethylene glycol)-b-poly(ethanedithiol-alt-nitrobenzyl)-b-poly(ethylene glycol) (PEG-b-PEDNB-b-PEG) is successfully prepared by sequential thiol-acrylate Michael addition polymerization in one pot. PEG-b-PEDNB-b-PEG is designed to have light-cleavable o-nitrobenzyl linkages and acid-labile ?-thiopropionate linkages positioned repeatedly in the main chain of the hydrophobic block. The light and pH dual degradation of PEG-b-PEDNB-b-PEG is traced by gel permeation chromatography (GPC). Such triblock copolymer can self-assemble into micelles, which can be used to encapsulate anticancer drug doxorubicin (DOX). Because of the different degradation chemistry of o-nitrobenzyl linkages and ?-thiopropionate linkages, DOX can be released from the micelles by two different manners, i.e., light-induced rapid burst release and pH-induced slow sustained release. Confocal laser scanning microscopy (CLSM) results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results show that the DOX-loaded micelles under UV light degradation exhibit better anticancer activity against A549 cells than that of the nonirradiated ones.
The UL49.5 gene of most herpesviruses is conserved and encodes glycoprotein N. However, the UL49.5 protein of duck enteritis virus (DEV) (pUL49.5) has not been reported. In the current study, the DEV pUL49.5 gene was first subjected to molecular characterization. To verify the predicted intracellular localization of gene expression, the recombinant plasmid pEGFP-C1/pUL49.5 was constructed and used to transfect duck embryo fibroblasts. Next, the recombinant plasmid pDsRed1-N1/ glycoprotein M (gM) was produced and used for co-transfection with the pEGFP-C1/pUL49.5 plasmid to determine whether DEV pUL49.5 and gM (a conserved protein in herpesviruses) colocalize. DEV pUL49.5 was thought to be an envelope glycoprotein with a signal peptide and two transmembrane domains. This protein was also predicted to localize in the cytoplasm and endoplasmic reticulum with a probability of 66.7%. Images taken by a fluorescence microscope at different time points revealed that the DEV pUL49.5 and gM proteins were both expressed in the cytoplasm. Overlap of the two different fluorescence signals appeared 12 h after transfection and continued to persist until the end of the experiment. These data indicate a possible interaction between DEV pUL49.5 and gM.
Oligodendrocytes are generated by the differentiation and maturation of oligodendrocyte precursor cells (OPCs). The failure of OPC differentiation is a major cause of demyelinating diseases; thus, identifying the molecular mechanisms that affect OPC differentiation is critical for understanding the myelination process and repairing after demyelination. Although prevailing evidence shows that OPC differentiation is a highly coordinated process controlled by multiple extrinsic and intrinsic factors, such as growth factors, axon signals, and transcription factors, the intracellular signaling in OPC differentiation is still unclear. Here, we showed that glycogen synthase kinase 3? (GSK3?) is an essential positive modulator of OPC differentiation. Both pharmacologic inhibition and knockdown of GSK3? remarkably suppressed OPC differentiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assays and Ki67 staining showed that the effect of GSK3? on OPC differentiation was not via cell death. Conversely, activated GSK3? was sufficient to promote OPC differentiation. Our results also demonstrated that the transcription of myelin genes was regulated by GSK3? inhibition, accompanying accumulated nuclear ?-catenin, and reduced the expression of transcriptional factors that are relevant to the expression of myelin genes. Taken together, our study identified GSK3? as a profound positive regulator of OPC differentiation, suggesting that GSK3? may contribute to the inefficient regeneration of oligodendrocytes and myelin repair after demyelination.
Nowadays, cancer is one of the most fatal threatens to human health. By utilizing the differences of cell environment between cancer cells and their normal counterparts as assembly-disassembly triggers, various smart drug nanocarriers have been designed to fight the cancer. Nevertheless, most of them are still not robust enough. One important reason is that they merely focus on a single stimulus. Thus, in order to achieve a better therapeutic effect, constructing multi responsive polymers is of great significance. However, most of multi responsive polymers used, up until now, are mainly based on block polymers synthesized via traditional polymerization methods, which are relatively time-consuming and laborious. Here in this article, a facile strategy preparing smart polymers with dual responsiveness (endosomal pH and over produced H2O2) was proposed and realized by orthogonal assembly of ?-CD-hydrazone-DOX and PEG-Fc. The obtained polymers were found to be able to spontaneously assemble into micelles in water, indicating their potential applications as drug nanocarriers. In vitro study revealed that the release of the encapsulated DOX was significantly enhanced by both H2O2 and low pH at 5.0. Furthermore, fluorescence microscopy and flow cytometry analysis showed that the assembled supramolecular prodrug micelles could be internalized into cancer cells. These properties suggested their promising application in cancer therapy.
Primary testicular lymphoma (PTL) accounts for ~1% of all non-Hodgkin's lymphomas and has a marked tendency for systemic relapse. The current study presents a unique case of testicular diffuse large B-cell lymphoma of non-germinal center B-cell subtype, with subcutaneous masses as the sole manifestation of the first relapse and central nervous system lymphoma as the second relapse. Subcutaneous relapse and subsequent brain relapse are extremely rare signs of PTL dissemination. The patient received methotrexate-based combined chemotherapy and achieved a partial response. This case presents a rare pattern of treatment failure in this malignant clinical entity.
Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biological functions and have been extensively investigated in past years.
Stimulation of Toll?like receptor 9 (TLR9) has been associated with invasion in various types of cancer cell in vitro. The present study aimed to evaluate the expression of TLR9 in MGC803 gastric cancer cells and investigate the effect of a non?specific TLR9 inhibitor, chloroquine (CQ), on MGC803 cell migration via the TLR9/nuclear factor kappa B (NF?B) signaling pathway. The expression of TLR9 was investigated using reverse transcription polymerase chain reaction (RT?PCR), flow cytometry and western blot analysis. The effects of CQ on MGC803 cell proliferation were measured by MTT colorimetric assay. The mRNA expression levels of cyclooxygenase?2 (COX?2), matrix metalloproteinase (MMP)?2, MMP?7 and NF?B p65 were evaluated by RT?PCR in MGC803 cells stimulated by various concentrations of CQ. The migration of gastric cancer cells treated with CQ at 12, 24 and 36 h was measured by wound healing assay. The results indicated that MGC803 cells expressed TLR9 and that CQ had anti?proliferative effects on MGC803 cells and inhibited mRNA expression of COX?2, MMP?2, MMP?7 and NF?B p65 (P<0.05). Furthermore, CQ inhibited the bioactivity of NF?B p65 and prevented the migration of MGC803 cells in a dose?dependent manner (P<0.05). In conclusion, the results indicated that the TLR9/NF?B signaling pathway was involved in gastric cancer cell migration and that CQ had anti?tumor activity.
Extended-spectrum beta-lactamases (ESBL)-producing Salmonella enterica have been reported worldwide. However, research on foodborne ESBL-producing Salmonella has been rarely conducted. One hundred and thirty eight ceftriaxone or/and cefoperazone-resistant Salmonella strains recovered from retail foods in Shaanxi and Henan Province, China, were screened for ESBL. The ESBL-producing strains were further characterized for antimicrobial resistance, pulse field gel electrophoresis (PFGE) profiles, and the presence of blaTEM, blaSHV, blaOXA, blaCTX-M, and blaPSE. The transferability of ESBL encoding genes to a susceptible Escherichia coli strain was also investigated. Thirty (21.7%) isolates were identified as ESBL positive and belonged to S. enterica serovars Indiana, Shubra, Typhimurium, and Enteritidis. S. Indiana and S. Shubra isolates were firstly identified in ESBL-producing strains. Great genetic diversity was seen among these ESBL-producing strains. Nucleotide sequence analysis revealed that blaTEM-1B was the only ESBL-encoding gene among the genes tested and was detected in 26 of 30 strains and was carried in the conjugative plasmids. The blaTEM-1B gene was transferable through conjugation at rates ranging from 4.71 × 10(-7) to 7.55 × 10(-6) transconjugant per recipient cell. This study provides the evidence of foodborne ESBL-producing Salmonella, and the transferability of plasmid harboring ESBL-encoding genes could possibly contribute to the dissemination of ESBL.
Hydrocerussite (Pb3(CO3)2(OH)2) is widely observed as a corrosion product in drinking water distribution systems. Its equilibrium solubility and dissolution rate can control lead concentrations in drinking water. The dissolution rate of hydrocerussite was investigated as a function of pH, dissolved inorganic carbon (DIC), and orthophosphate concentrations at conditions relevant to drinking water distribution using continuously stirred tank reactors (CSTRs). In the absence of DIC and orthophosphate, the dissolution rate decreased with increasing pH. Addition of DIC inhibited the dissolution of hydrocerussite. The addition of orthophosphate significantly decreased the dissolution rate of hydrocerussite. At conditions with orthophosphate and without DIC, a lead(II) phosphate solid hydroxylpyromorphite (Pb5(PO4)3OH) was observed after reaction, and orthophosphate's inhibitory effect can be attributed to the formation of this low-solubility lead(II) phosphate solid. In the presence of both orthophosphate and DIC, no lead(II) phosphate solid was observed, but the rate was still lowered by the presence of orthophosphate, which might be due to the adsorption of orthophosphate to block reactive sites on the hydrocerussite surface. For systems in which hydroxylpyromorphite was present, the steady-state effluent lead concentrations from the CSTRs were close to the predicted equilibrium solubility of hydroxylpyromorphite. In the absence of orthophosphate rapid equilibration of hydrocerussite was observed.
Mucoepidermoid carcinoma (MEC) is common in human salivary glands. Surgery is the preferred treatment method for MEC and chemotherapy is often administered following surgery as an adjuvant cancer treatment; however, chemotherapy does not completely prevent tumor recurrence. Emerging evidence has indicated the existence of cancer stem-like (CSL)-cells in tumors. CSL-cells are important in the development, invasion and drug resistance of carcinomas. The present study aimed to investigate whether chemotherapy enriched the CSL-cells in the MEC cell line of MC3 using 5-fluorouracil (5-Fu). The MC3 cells were treated with 5-Fu, which enhanced the spherogenesis and vitality of the cells and upregulated the pluripotency gene, octamer-binding transcription factor 4. Side population analysis demonstrated that the proportion of CSL-cells also increased. These findings showed that compared with other types of cancer cells, chemotherapy was unable to effectively kill the CSL-cells resulting in an enriched CSL-cell subpopulation with a higher resistance to chemotherapy, which may have been key the recurrence of MEC.
The Toll-like receptor 9 (TLR9) plays a crucial role in both innate and adaptive immune responses against infection and danger signals. Stimulation of TLR9 has been linked to invasion in various cancer cells in vitro. The present study evaluated the expression of TLR9 in human esophageal cancer (EC) cells and normal and malignant esophageal squamous epithelium, and examined the association between TLR9 expression, clinicopathological variables, and EC patient outcome. We further characterized the direct effects of TLR9 agonist CpG oligonucleotides (CpG ODN) and inhibitor chloroquine (CQ), on the proliferation and invasion of EC cells in vitro. RT-PCR, western blot, flow cytometry and immunohistochemical analysis were used to determine the expression of TLR9 in EC cell line TE10, and 90 cases of esophageal squamous cell carcinoma, including 30 cases of adjacent esophageal epithelium. The TLR9 expression was compared with tumor size, location, grade, stage and proliferation. We found basal expression of TLR9 in TE10 cells. Esophageal carcinomas exhibited TLR9 expression that was positively associated with tumor size, location and TNM stage (P<0.05). CpG ODN significantly enhanced the invasion of TE10 cells, which could be abrogated by a TLR9 inhibitor CQ. CpG ODN led to activation of NF??B and enhanced expression of matrix metalloproteinase (MMP)-2, MMP-7 and cyclooxygenase-2 (COX-2) mRNA. Expression of TLR9 in EC suggests a role of TLR9 related to cell proliferation and differentiation. Our findings indicate that TLR9 may represent a novel therapeutic target in this disease.
We present a nonparametric shape constrained algorithm for segmentation of coronary arteries in computed tomography images within the framework of active contours. An adaptive scale selection scheme, based on the global histogram information of the image data, is employed to determine the appropriate window size for each point on the active contour, which improves the performance of the active contour model in the low contrast local image regions. The possible leakage, which cannot be identified by using intensity features alone, is reduced through the application of the proposed shape constraint, where the shape of circular sampled intensity profile is used to evaluate the likelihood of current segmentation being considered vascular structures. Experiments on both synthetic and clinical datasets have demonstrated the efficiency and robustness of the proposed method. The results on clinical datasets have shown that the proposed approach is capable of extracting more detailed coronary vessels with subvoxel accuracy.
Gene regulatory networks (GRNs) coherently coordinate the expressions of genes and control the behaviors of cellular systems. The complexity in modeling a quantitative GRN usually results from inaccurate parameter estimation, which is mostly due to small sample sizes. For better modeling of GRNs, we have designed a small-sample iterative optimization algorithm (SSIO) to quantitatively model GRNs with nonlinear regulatory relationships. The algorithm utilizes gene expression data as the primary input and it can be applied in case of small-sized samples. Using SSIO, we have quantitatively constructed the dynamic models for the GRNs controlling human and mouse adipogenesis. Compared with two other commonly-used methods, SSIO shows better performance with relatively lower residual errors, and it generates rational predictions on the adipocyte responses to external signals and steady-states. Sensitivity analysis further indicates the validity of our method. Several differences are observed between the GRNs of human and mouse adipocyte differentiations, suggesting the differences in regulatory efficiencies of the transcription factors between the two species. In addition, we use SSIO to quantitatively determine the strengths of the regulatory interactions as well as to optimize regulatory models. The results indicate that SSIO facilitates better investigation and understanding of gene regulatory processes.
Stomatal pores surrounded by a pair of guard cells in the plant epidermis control gas exchange between plants and the atmosphere in response to light, CO2, and the plant hormone abscisic acid. Light-induced stomatal opening is mediated by at least three key components: the blue light receptor phototropin (phot1 and phot2), plasma membrane H(+)-ATPase, and plasma membrane inward-rectifying K(+) channels. Very few attempts have been made to enhance stomatal opening with the goal of increasing photosynthesis and plant growth, even though stomatal resistance is thought to be the major limiting factor for CO2 uptake by plants. Here, we show that transgenic Arabidopsis plants overexpressing H(+)-ATPase using the strong guard cell promoter GC1 showed enhanced light-induced stomatal opening, photosynthesis, and plant growth. The transgenic plants produced larger and increased numbers of rosette leaves, with ?42-63% greater fresh and dry weights than the wild type in the first 25 d of growth. The dry weights of total flowering stems of 45-d-old transgenic plants, including seeds, siliques, and flowers, were ?36-41% greater than those of the wild type. In addition, stomata in the transgenic plants closed normally in response to darkness and abscisic acid. In contrast, the overexpression of phototropin or inward-rectifying K(+) channels in guard cells had no effect on these phenotypes. These results demonstrate that stomatal aperture is a limiting factor in photosynthesis and plant growth, and that manipulation of stomatal opening by overexpressing H(+)-ATPase in guard cells is useful for the promotion of plant growth.
Rhenium-catalyzed oxyalkylation of alkenes is described, where hypervalent iodine(III) reagents derived from widely occurring aliphatic carboxylic acids were used as, for the first time, not only an oxygenation source but also an alkylation source via decarboxylation. The reaction also features a wide substrate scope, totally regiospecific difunctionalization, mild reaction conditions, and ready availability of both substrates. Mechanistic studies revealed a decarboxylation/radical-addition/cation-trapping cascade operating in the reaction.
Bamboo charcoal (BC) was used as starting material to prepare iron-modified bamboo charcoal (Fe-MBC) by its impregnation in FeCl3 and HNO3 solutions simultaneously, followed by microwave heating. The material can be used as an adsorbent for Pb(II) contaminants removal in water. The composites were prepared with Fe molar concentration of 0.5, 1.0 and 2.0 mol/L and characterized by means of N2 adsorption-desorption isotherms, X-ray diffraction spectroscopy (XRD), scanning electron microscopy coupled with energy dispersive X-ray spectrometry (SEM-EDS), Fourier transform infrared (FT-IR) and point of zero charge (pH(pzc)) measurements. Nitrogen adsorption analyses showed that the BET specific surface area and total pore volume increased with iron impregnation. The adsorbent with Fe molar concentration of 2 mol/L (2Fe-MBC) exhibited the highest surface area and produced the best pore structure. The Pb(II) adsorption process of 2Fe-MBC and BC were evaluated in batch experiments and 2Fe-MBC showed an excellent adsorption capability for removal Pb(II). The adsorption of Pb(II) strongly depended on solution pH, with maximum values at pH 5.0. The ionic strength had a significant effect on the adsorption at pH < 6.0. The adsorption isotherms followed the Langmuir isotherm model well, and the maximum adsorption capacity for Pb(II) was 200.38 mg/g for 2Fe-MBC. The adsorption processes were well fitted by a pseudo second-order kinetic model. Thermodynamic parameters showed that the adsorption of Pb(II) onto Fe-MBC was feasible, spontaneous, and exothermic under the studied conditions, and the ion exchange mechanism played an significant role. These results have important implications for the design of low-cost and effective adsorbents in the removal of Pb(II) from wastewater.
Accumulating evidence suggests that microRNAs (miRNAs) contribute to a myriad of kidney diseases. However, the regulatory role of miRNAs on the key molecules implicated in kidney fibrosis remains poorly understood. Bone morphogenetic protein-7 (BMP-7) and its related BMP-6 have recently emerged as key regulators of kidney fibrosis. Using the established unilateral ureteral obstruction (UUO) model of kidney fibrosis as our experimental model, we examined the regulatory role of miRNAs on BMP-7/6 signaling. By analyzing the potential miRNAs that target BMP-7/6 in silica, we identified miR-22 as a potent miRNA targeting BMP-7/6. We found that expression levels of BMP-7/6 were significantly elevated in the kidneys of the miR-22 null mouse. Importantly, mice with targeted deletion of miR-22 exhibited attenuated renal fibrosis in the UUO model. Consistent with these in vivo observations, primary renal fibroblast isolated from miR-22-deficient UUO mice demonstrated a significant increase in BMP-7/6 expression and their downstream targets. This phenotype could be rescued when cells were transfected with miR-22 mimics. Interestingly, we found that miR-22 and BMP-7/6 are in a regulatory feedback circuit, whereby not only miR-22 inhibits BMP-7/6, but miR-22 by itself is induced by BMP-7/6. Finally, we identified two BMP-responsive elements in the proximal region of miR-22 promoter. These findings identify miR-22 as a critical miRNA that contributes to renal fibrosis on the basis of its pivotal role on BMP signaling cascade.
Eye gaze is a powerful signal, which exerts a mixture of arousal, attentional, and social effects on the observer. We recently found a behavioural interaction between eye contact and mimicry where direct gaze rapidly enhanced mimicry of hand movements ). Here, we report two detailed investigations of this effect. In Experiment 1, we compared the effects of "direct gaze", "averted gaze", and "gaze to the acting hand" on mimicry and manipulated the sequence of gaze events within a trial. Only direct gaze immediately before the hand action enhanced mimicry. In Experiment 2, we examined the enhancement of mimicry when direct gaze is followed by a "blink" or by "shut eyes", or by "occluded eyes". Enhanced mimicry relative to baseline was seen only in the blink condition. Together, these results suggest that ongoing social engagement is necessary for enhanced mimicry. These findings allow us to place the gaze-enhancement effect in the context of other reported gaze phenomena. We suggest that this effect is similar to previously reported audience effects, but is less similar to ostensive cueing effects. This has important implications for our theories of the relationships between social cues and imitation.
Excessive extracellular glutamate leads to neuronal death in central nervous system. Excitatory glutamate transporter subtype 2 (GLT-1) carries bulk of glutamate reuptake in cerebral ischemia. Although GLT-1 expression fluctuates during the period of ischemia, little is known about its regulatory mechanism. Here we show an up-regulation of GLT-1 via mammalian target of rapamycin (mTOR)-Akt-nuclear factor-?B (NF-?B) signaling cascade in oxygen glucose deprivation (OGD). We found that brief rapamycin treatment significantly increased GLT-1 expression in cultured astrocytes. Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. This conclusion was further confirmed by raptor and rictor disruption experiments. Akt was activated by mTORC1 inhibition and required for GLT-1 expression because triciribine, a specific inhibitor of Akt, blocked the increase of GLT-1 expression. mTOR-Akt cascade then activated NF-?B and increased ?B-motif-binding phosphoprotein (KBBP) expression and GLT-1 transcription. We next demonstrated that mTOR-Akt-NF-?B cascade was activated in OGD and subsequently caused the upregulation of GLT-1. Supporting evidence included: (1) inhibition of Akt or NF-?B occluded OGD-induced GLT-1 upregulation; (2) Raptor knock-down plus OGD did not add to the increase of GLT-1 expression; (3) Intact mTORC2 was required for GLT-1 enhancement. In summary, our data first showed that mTOR-Akt-NF-?B cascade played critical roles to up-regulate GLT-1 in OGD. This signaling cascade may work to promote glutamate uptake in brain ischemia and neurodegenerative diseases.
Abstract Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are progressive neurodegenerative disorder associated with polygenetic, maternally inherited mutations in mitochondrial DNA. Approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial tRNA(Leu (UUR)) gene (MT-TL1). We reported two probands with MELAS features. Muscle biopsy identified ragged-red fibers (RRF) in Gomori Trichrome staining. A respiratory chain function study showed decreased activity of mitochondrial respiratory chain complex I in both probands. Sequencing of the mitochondrial DNA revealed two novel MT-ND1 gene missense mutations, m.3959G>A and m.3995A>G, which are highly conserved among species. Protein secondary structure predictions demonstrated that these mutations may alter the peptide structure and may lead to decreased ND1 gene stability. Our findings suggest that these two novel mutations may contribute to the MELAS phenotypes of the patients in our study.
For the first time, pseudopolyrotaxane prodrug micelles with high drug content were prepared in water, which could be used for cancer therapy. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.
Studies evaluating the diagnostic performance of coronary computed tomography angiography (CTA) are consistent in demonstrating a high negative predictive accuracy, but only a modest positive predictive accuracy for the detection of significant coronary artery disease. Consequentially, there has been a considerable effort made to enhance the diagnostic capability of coronary CTA by developing scanner technology and also post-processing algorithms for coronary stenosis evaluation. Of these new developments, the proposition of being able to measure non-invasive fractional flow reserve by coronary computed tomography angiography (FFRct) has generated much recent interest. Initial reports indicate that the application FFRct not only correlates well with invasive fractional flow reserve but also has the potential to enhance substantially the positive predictive accuracy and overall accuracy of coronary CTA. Although it is theoretically possible to measure FFRct using complex computational fluid dynamics adapted from the aeronautical industry, this approach is likely to face a number of challenges prior to it being accepted into the mainstream as an adjunct to coronary CTA. The aim of the current review is to provide an overview of: 1) the fundamental engineering principles behind computational fluid dynamic modelling of coronary arterial blood flow; 2) the difficulties faced from an engineering perspective in developing a truly representative model; and 3) the challenges this technology is likely to face as it attempts to enter the clinical domain.
Forkhead box protein 3 (Foxp3) is known as a specific marker for regulatory T cells which contribute to immunosuppression in tumor microenvironment. However, existing studies regarding clinical significance of Foxp3+ tumor-infiltrating lymphocytes (TILs) in glioblastoma (GBM) remained discrepant. In this study, we aimed to explore whether this subtype of TILs correlated with prognosis in patients with GBM. Foxp3+ TILs as well as CD8+ ones were detected by immunohistochemistry on paraffin-embedded tumor samples from 62 patients. Staining for p53, MGMT and Ki-67 were also performed. The correlation of TIL subtypes with clinicopathologic features were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared using log-rank test. Independent prognostic factors for PFS and OS were determined through univariate and multivariate analysis. Significant correlation was found between Foxp3 and CD8 expression (P = 0.003), but not between TIL subtypes and clinicopathologic characteristics. Patients with higher density of Foxp3+ TILs showed relatively shorter PFS (P < 0.001) and OS (P = 0.003) whereas patients with higher density of CD8+ TILs obtained no significant differences in survival. Survival analysis based on molecular classifications further clarified these predictive values. Univariate and multivariate analysis revealed that frequency of Foxp3+ TILs was probably associated with both PFS (P = 0.002) and OS (P = 0.003). In conclusion, the results suggest that Foxp3 positive infiltrates could provide an independent predictive factor in GBM.
Even at present it is still difficult to characterize the reaction between CO2 and Ca(OH)2 at high temperature and atmospheric pressure using traditional instruments such as thermogravimetric analyzer and differential scanning calorimeter. This study was devoted to characterizing such a reaction in a newly developed micro fluidized bed reaction analyzer (MFBRA) under isothermal conditions in the temperature range of 773-1023 K. The results indicated that the MFBRA has not only a good adaptability for characterizing the above-mentioned reaction but enables as well a new insight into the mechanism of the reaction. An obvious time delay was identified for the release of the formed steam (H2O) in comparison with the onset of its CO2 absorption, which might be attributed to the formation of an unstable intermediate product Ca(HCO3)2 in the reaction process between CO2 and Ca(OH)2. The activation energy for forming Ca(HCO3)2 was found to be about 40 kJ/mol, which is much lower than that of the reaction between CO2 and CaO.
Neural stem/progenitor cells (NSPCs) of the subgranular zone have been implicated in cognitive processes, which represent a potentially important source of regenerative medicine for the treatment of neurodegenerative diseases such as Alzheimers disease (AD). In our previous studies, ZY-1, a novel nicotinic analog, improved cognitive function in transgenic mice model of AD. However, the effect of ZY-1 on the NSPCs remains unclear. Here, we show that ZY-1 significantly increased proliferation and migration of NSPCs, but failed to affect NSPCs differentiation in vitro. Furthermore, during the proliferative period, ZY-1 enhanced intracellular reactive oxygen species (ROS) levels. Meanwhile, ZY-1 also inhibited the levels of A?42-induced ROS. Our data indicate that ZY-1 regulates adult hippocampal neurogenesis in vitro, at least partly due to modulating intracellular ROS levels. These results, taken together with those of our previous studies, suggest that ZY-1 might have a potential therapeutic effect for the treatment of AD.
The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1 mM pyruvate and oxaloacetate (Pyr/Oxa) for 1 h decreased blood glutamate levels by ?50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, in vivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions.
ZnO coupled TiO2/bamboo charcoal (ZnO-TiO2/BC) was prepared using the sol-gel method combined with microwave irradiation. The ZnO-TiO2/BC and TiO2/BC were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), N2 adsorption (BET), and UV-vis diffuse reflectance spectroscopy (UV-vis-DRS). The ZnO dopant promoted the transformation of anatase TiO2 to rutile phase, and a significant red shift of absorption edge was brought out due to the interfacial coupling effect between ZnO and TiO2 particles. The BET specific surface area and total pore volume decreased with ZnO doping, indicating that some micropores were blocked. SEM studies indicated that ZnO was almost uniformly deposited on the surface of the ZnO-TiO2/BC. The adsorption and photocatalytic degradation experiments showed that the photo-degrade efficiency for Zno-TiO2/BC was higher than that of TiO2/BC, and for both composites, the removal efficiency of HA increased as pH decreased from 10.0 to 2.0. The degradation of HA by ZnO-TiO2/BC and TiO2/BC fitted well with the Langmuir-Hinshelwood kinetics model, and HA degradation was achieved through a synergistic mechanism of adsorption and photocatalysis. ZnO-TiO2/BC could be used as an effective and alternative photocatalyst for the treatment of water contaminated by organic pollutants.
In Lafora disease (LD), the deficiency of either EPM2A or NHLRC1, the genes encoding the phosphatase laforin and E3 ligase, respectively, causes massive accumulation of less-branched glycogen inclusions, known as Lafora bodies, also called polyglucosan bodies (PBs), in several types of cells including neurons. The biochemical mechanism underlying the PB accumulation, however, remains undefined. We recently demonstrated that laforin is a phosphatase of muscle glycogen synthase (GS1) in PBs, and that laforin recruits malin, together reducing PBs. We show here that accomplishment of PB degradation requires a protein assembly consisting of at least four key enzymes: laforin and malin in a complex, and the glycogenolytic enzymes, glycogen debranching enzyme 1 (AGL1) and brain isoform glycogen phosphorylase (GPBB). Once GS1-synthesized polyglucosan accumulates into PBs, laforin recruits malin to the PBs where laforin dephosphorylates, and malin degrades the GS1 in concert with GPBB and AGL1, resulting in a breakdown of polyglucosan. Without fountional laforin-malin complex assembled on PBs, GPBB and AGL1 together are unable to efficiently breakdown polyglucosan. All these events take place on PBs and in cytoplasm. Deficiency of each of the four enzymes causes PB accumulation in the cytoplasm of affected cells. Demonstration of the molecular mechanisms underlying PB degradation lays a substantial biochemical foundation that may lead to understanding how PB metabolizes and why mutations of either EPM2A or NHLRC1 in humans cause LD. Mutations in AGL1 or GPBB may cause diseases related to PB accumulation.
The purpose of this study was to identify characteristic magnetic resonance imaging (MRI) features of cerebral sparganosis, a rare parasitic disease caused by the plerocercoid larva of Spirometra mansoni.
The mechanism by which chlamydiae persist in vivo remains undefined; however, chlamydiae in most animals persist in the gastrointestinal tract (GI) and are transmitted via the fecal-oral route. Oral infection of mice with Chlamydia muridarum was previously shown to establish a long-term persistent infection in the GI tract. In this study, BALB/c, DBA/2, and C57Bl/6 mice, infected orally with C. muridarum, were infected in the cecum for as long as 100 days in the absence of pathology. The primary target tissue was the cecum although the large intestine was also infected in most animals. A strong serum IgG and cecal IgA antibody response developed. Lymphocyte proliferation assays to chlamydial antigen on mesenteric lymph node cells were positive by day 10 and peaked on days 15-21, but the response returned to baseline levels by 50 days, despite the ongoing presence of the organism in the cecum. Because studies have shown that women and men become infected orally with chlamydiae, we propose that the GI tract is a site of persistent infection and that immune down-regulation in the gut allows chlamydiae to persist indefinitely. As a result, women may become reinfected via contamination of the genital tract from the lower GI tract.
Reduced arterial compliance is associated with an increased rate of morbidity and mortality in cardiovascular disease. Exercise is beneficial for compromised arterial compliance. However, the beneficial effects of exercise are lost with exhaustion. Lycium barbarum L. has been used in China for centuries to maintain good health. In this regard, the primary purpose of this study was to characterize the effects of the polysaccharides from Lycium barbarum (LBPs) on arterial compliance during exhaustive exercise.
Duck enteritis virus (DEV) UL49.5 encoding glycoprotein N was a conserved gene. The transcription dynamic process of UL49.5 homologous genes in herpesviruses was reported. However, the transcription dynamic process of DEV UL49.5 gene has not yet been established. In this study, a real-time quantitative reverse transcription PCR (real-time qRT-PCR) assay was established to test the transcription dynamic process of DEV UL49.5 gene, and the recombinant plasmid pUCm-T/UL49.5 was constructed as the standard DNA. The samples prepared from DEV-infected (at different time points) and uninfected cell were detected and calculated. The results demonstrated that the real-time qRT-PCR assay was successfully established. The transcription product of DEV UL49.5 gene was first detected at 0.5 h post infection (p.i.), increased at 8 h p.i. and reached a peak at 60 h p.i. Our results illustrated that DEV UL49.5 gene could be regarded as a late gene. The transcription dynamic process of DEV UL49.5 gene may provide a significant clue for further studies of DEV UL49.5 gene.
Precise and effective genome-editing tools are essential for functional genomics and gene therapy. Targeting nucleases have been successfully used to edit genomes. However, whole-locus or element-specific deletions abolishing transcript expression have not previously been reported. Here, we show heritable targeting of locus-specific deletions in the zebrafish nodal-related genes squint (sqt) and cyclops (cyc). Our strategy of heritable chromosomal editing can be used for disease modeling, analyzing gene clusters, regulatory regions, and determining the functions of non-coding RNAs in genomes.
Multinucleated cells are present in impaired spermatogenesis and in the senescent testis. Following accumulating evidence from our previous studies on the identification of multinucleated cells during normal testicle development, the current study further investigated the possible mechanism and role of these multinucleated cells. Healthy male Kunming mice were used in the present study. The association between multinucleated cells and cell apoptosis were analyzed using TUNEL analysis and immunohistochemistry. The results showed that multinucleated cells are widespread in the testicular tissue of seminiferous tubules on postnatal days 23, 27, 30, 33, 36, 40, 47, 50 and 54 suggesting that these cells are involved in the process of normal development of mouse testis. Histochemical analysis revealed a lack of proliferating cell nuclear antigen, cyclin D1 protein expression in multinucleated cells, suggesting that these cells are not involved in the G1 and S phases of the cell cycle and cell proliferation. Increased expression of Bax and caspase 3 was detected, revealing that multinucleated cells may be associated with cell apoptosis during testicular development. To the best of our knowledge, this study demonstrated for the first time that multinucleated cells are present during normal testicular development and may be associated with spermatogonial stem cell apoptosis. Therefore, multinucleated cells may be important in the spermatogenesis process.
Hip fracture incidence rates in Hefei, China, over a period of 1 year (2010) were assessed. The aim of this study was to investigate the incidence and epidemiology of hip fracture in Hefei and compare it with other populations. All the hip fracture records were obtained from the Hefei Hospital Discharge Register for the entire population ?50 years of age and restricted to cervical or trochanteric types. The incidence of hip fracture was standardized to the 2010 World population. A total of 1518 (aged ?50) hip fractures (628 in men, 890 in women) were recorded during the study period. The age-adjusted incidence rate for 1 year was 144/100,000 (95 % CI = 135-153/100,000) for women and 97/100,000 (95 % CI = 85-109/100,000) for men. The standardized incidence rate against the 2010 World population was 151.7/100,000 for women and 98.2/100,000 for men. The mean age of patients with a hip fracture was 74.5 ± 10.1 years for women and 71.9 ± 11.9 years for men. The overall female to male ratio of hip fracture was 1.48:1 for hip fracture incidence and 1.54:1 for standardized incidence. Simple fall accounted for 85 % hip fractures in total cases. Hefei has a lower incidence of hip fracture compared with Beijing and other countries from the five continents in recent studies, but a higher incidence than those cities in north-east China in the early 1990s. The inequality incidence in different geographic areas could be due to the urbanization or life expectancy of the population, but further investigation needs to be done to confirm this hypothesis. We also found a higher incidence in women than in men. Simple fall may be the main mechanism of injury for hip fracture.
Previous studies show that X-ray cross-complementing group 1 (XRCC1) Arg194Trp may result in variations in hosts repair efficiency of DNA damage, and this repair deficit may eventually cause individual susceptibility to oral cancer. However, published data regarding the association between XRCC1 Arg194Trp polymorphism and oral cancer risk were contradictory. The aim of this study was to derive a more precise estimation of the association of XRCC1 Arg194Trp polymorphism with oral cancer by performing a meta-analysis. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Finally, a meta-analysis of nine eligible studies including 1,281 cases and 1,966 controls was performed. Overall, there was a significant association between XRCC1 Arg194Trp polymorphism and oral cancer risk (for Trp versus Arg: OR = 1.41, 95 % CI 1.08-1.83, P = 0.01; for TrpTrp versus ArgArg: OR = 1.50, 95 % CI 1.00-2.30, P = 0.05; for TrpTrp/ArgTrp versus ArgArg: OR = 1.49, 95 % CI 1.14-1.94, P = 0.003). After excluding those studies containing patients with oral leukoplakia, there was still an obvious association between XRCC1 Arg194Trp polymorphism and oral cancer risk (for TrpTrp/ArgTrp versus ArgArg: OR = 1.40, 95 % CI 1.14-1.71, P = 0.001). Subgroup analysis by ethnicity suggested that there was an obvious association between XRCC1 Arg194Trp polymorphism and oral cancer risk in Asians under three genetic models. In conclusion, the results from this meta-analysis suggest that XRCC1 Arg194Trp polymorphism is associated with oral cancer risk, especially in Asians.
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