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High diversity and differential evolution profiles have been observed for DD34E/ Tc1 transposons; several families originating from these groups, such as DD34E/ ZB , DD34E/ SB , DD35E/ TR , DD36E/ IC, and DD38E/ IT , have been well defined. Even though Frisky , Tiang , Tsessebe, and Topi transposons have been identified in Anopheles gambiae , their taxonomic distribution and phylogenetic relationship in nature remain largely unknown. The evolutionary profiles of Frisky , Tiang , Tsessebe , and Topi homology transposons were investigated in the current study. In total, 254 homology transposons of Frisky , Tiang , Hob , Tsessebe, and Topi were obtained in 200 species by data mining. The phylogenetic tree revealed that these transposons were classified into five main clades (Frisky , Tiang , Hob , Tsessebe , and Topi) forming a monophyletic clade with 98% bootstrap support, belonging to the DD34E/ Tc1 group, and named as Skipper (SK). SK transposons show a wide distribution in animals; however, differential taxonomic distribution patterns were observed for the subfamilies of Frisky , Tiang , Hob , Tsessebe, and Topi ; extensive invasion of Frisky in animals was found, whereas Tiang , Hob , Tsessebe, and Topi were mainly detected in Diptera. SK elements share a similar structural organization and display high sequence identities across subfamilies. Evolutionary dynamics and structural analysis revealed that SK s in some species, such as Bombyx mori , Lordiphosa magnipectinata , Carassius gibelio , Triplophysa dalaica , and Silurus glanis , have recently evolved and present as intact copies, indicating that SK s in these genomes may be active. Together, these observations improve our understanding of the diversity of DD34E/ Tc1 transposons and their impacts on genome evolution in animals. [ABSTRACT FROM AUTHOR]

AIM: To investigate the role of Ywhab in the growth of mouse B-cell lymphoma, and to explore the potential underlying mechanisms. METHODS : The correlation between Ywhab and human diffuse large B-cell lymphoma (DLBCL) was investigated by bioinformatics analysis. Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene, which was verified by RT-qPCR and Western blot. The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting, CCK-8 assay, and subcutaneous tumor loading experiments. The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot. Co-immunoprecipitation combined with mass spectrometry (CoIP-MS) was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β, which was confirmed by Western blot and molecular docking analysis. RESULTS: The Ywhab gene exhibited low expression in DLBCL, which was correlated with poor clinical prognosis of DLBCL patients. Compared with normal mouse bone marrow B cells, Ywhab expression was low in 38B9 cells. Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo, promoted the expression of pro-apoptotic proteins Puma, Noxa and Bax at both mRNA and protein levels, and inhibited the mRNA and protein expression of anti-apoptotic protein Bcl2 (P<0. 05). The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels, thereby suppressing the growth of 38B9 cells. CONCLUSION: Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1. [ABSTRACT FROM AUTHOR]

miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors. [ABSTRACT FROM AUTHOR]

α-synuclein (α-syn) is a highly conserved and thermostable protein that is widely distributed in human brain. An intracellular aggregation of α-syn in dopaminergic neurons is the hallmark of a group of neurodegenerative diseases including Parkinson's disease. Interestingly, α-syn is also highly expressed in red blood cells and is considered as one of the most abundant proteins in red blood cells. Moreover, α-syn is thought to play a regulatory role during normal erythropoiesis. However, whether α-syn participates in the pathogenesis of erythroid diseases has not been reported. In this review, we discuss the protein structure of α-syn and the importance of α-syn in erythropoiesis. [ABSTRACT FROM AUTHOR]

PAX5, a B cell-specific transcription factor, is overexpressed through chromosomal translocations in a sub-set of B cell lymphomas. Previously, we had shown that activation of immunoreceptor tyrosine-based activa-tion motif (ITAM) proteins and B cell receptor (BCR) signaling by PAX5 contributes to B-lymphomagenesis. However, the effect of PAX5 on other oncogenic transcription factor-controlled pathways is unknown. Using a MYC-induced murine lymphoma model as well as MYC-transformed human B cell lines, we found that PAX5 controls c-MYC protein stability and steady-state levels. This promoter-independent, posttranslational mechanism of c-MYC regulation was independent of ITAM/BCR activity. Instead it was controlled by another PAX5 target, CD19, through the PI3K-AKT-GSK3 β axis. Consequently, MYC levels in B cells from CD19-defi-cient mice were sharply reduced. Conversely, reexpression of CD19 in murine lymphomas with spontaneous silencing of PAX5 boosted MYC levels, expression of its key target genes, cell proliferation in vitro, and over-all tumor growth in vivo. In human B-lymphomas, CD19 mRNA levels were found to correlate with those of MYC-activated genes. They also negatively correlated with the overall survival of patients with lymphoma in the same way that MYC levels do. Thus, CD19 is a major BCR-independent regulator of MYC-driven neoplastic growth in B cell neoplasms., Introduction The concept of oncogene addiction (1) is particularly well validated in hematological malignancies. 'Liquid' tumors are thought to depend on fewer genetic alterations and thus be more sensitive to [...]

Nonstandard abbreviations used: BCR, B cell receptor; DLBCL, diffuse large B cell lymphoma; ITAM, immunoreceptor tyrosine-based activation motif; 4OHT, 4-hydroxytamoxifen; Pax5ERTAM, fusion of Pax5 and tamoxifen receptor; shRNA, short hairpin [...]

Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. Whether autophagy observed in treated cancer cells represents a mechanism that allows tumor cells [...]

This study aims at evaluating the importance and its underlying mechanism of the cluster of microRNA-144/451 (miR-144/451) in the models with intracerebral hemorrhage (ICH). A model of collagenase-induced mice with ICH and a model of mice with simple miR-144/451 gene knockout (KO) were used in this study. Neurodeficits and the water content of the brain of the mice in each group were detected 3 days after collagenase injection. The secretion of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), as well as certain biomarkers of oxidative stress, was determined in this study. The results revealed that the expression of miR-451 significantly decreased in the mice with ICH, whereas miR-144 showed no significant changes. KO of the cluster of miR-144/451 exacerbated the neurological deficits and brain edema in the mice with ICH. Further analyses demonstrated that the KO of the cluster of miR-144/451 significantly promoted the secretion of TNF-α and IL-1β and the oxidative stress in the perihematomal region of the mice with ICH. In addition, the miR-144/451's depletion inhibited the regulatory axis' activities of miR-451-14-3-3ζ-FoxO3 in the mice with ICH. In conclusion, these data demonstrated that miR-144/451 might protect the mice with ICH against neuroinflammation and oxidative stress by targeting the pathway of miR-451-14-3-3ζ-FoxO3. [ABSTRACT FROM AUTHOR]

To investigate the effects of Lycium barbarum polysaccharide (LBP) on pathological symptoms and behavioral deficits in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model. The therapeutic effects of LBP were monitored with an Open field test, a Rotarod test and a Morris water maze test. We also investigated the mechanisms with qRT-PCR and Western blotting analyses. After a relatively short-term LBP treatment, the total distance and walking time of PD mice significantly increased. The staying duration on the rod of PD mice increased in the Rotarod test. LBP can up-regulate levels of SOD2, CAT and GPX1 and inhibit the abnormal aggregation of α-synuclein induced by MPTP. LBP treatment can also up-regulate the phosphorylation of AKT and mTOR, and may play its protective role by activating the PTEN/AKT/mTOR signaling axis. These results suggest that LBP can effectively alleviate the degeneration in the nigrostriatal system induced by MPTP treatment. It may be a potential candidate for the treatment of Parkinson’s disease. [ABSTRACT FROM AUTHOR]

Several studies have shown that the isolated retrieval of a consolidated fear memory can induce a labile phase, during which extinction training can prevent the reinstatement, a form of relapse in which fear response to a fear-provoking context returns when a mild shock is presented. However, fear memory retrieval may also have another opposing result: the enhancement of fear memory. This implies that the fear memory trace can be modified by a brief retrieval. Unclear is whether the fear-impairing effect of retrieval-extinction (RE) is altered by a prior brief retrieval. The present study investigated the responses of recent and remote fear memories to the RE procedure after the presentation of an additional prior retrieval (priRet). We found that a single RE procedure effectively blocked the reinstatement of 2-day recent contextual fear memory. The memory-impairing effect of the RE procedure on recent fear was not observed when priRet was presented 6 or 24 h before the RE procedure. In contrast to the 2-day recent memory, the RE procedure failed to block the reinstatement of 36-day remote fear memory but successfully disrupted the return of remote fear memory after priRet. This memory-disruptive effect on remotememory did not occur when priRet was performed in a novel context. Nimodipine administration revealed that the blockade of priRet-induced processes recovered the effects of the RE procedure on both recent and remote fear memories. Our findings suggest that the susceptibility of recent and remote fear memories to RE procedures can be altered by an additional retrieval. [ABSTRACT FROM AUTHOR]

SRY-box 9 (SOX9) is an important transcription factor required for development, which has additionally been reported to be an independent prognostic indicator for the survival of patients with non-small cell lung cancer (NSCLC). Accumulating evidence has indicated that dysregulation of microRNAs (miRNAs/miRs) may contribute to the initiation and progression of cancer. SOX9 may be regulated by a number of miRNAs in different types of cancer, including in NSCLC. The present study sought to identify novel candidate miRNAs associated with SOX9 in NSCLC using online tools, and investigated the detailed functions of miR-185, which suppressed SOX9 mRNA expression most strongly out of the candidate miRNAs. It was observed that ectopic miR-185 expression significantly suppressed NSCLC cell proliferation, invasion and migration. Using luciferase reporter gene and RNA immunoprecipitation assays, SOX9 was confirmed to be a direct target of miR-185. In addition, the downstream Wnt signaling-associated factors β-catenin and c-Myc proto-oncogene protein (Myc) were demonstrated to be inhibited by miR-185 overexpression. SOX9, β-catenin and c-Myc mRNA expression was significantly upregulated in NSCLC tissues, and was inversely correlated with miR-185 expression. The results of the present study demonstrated that rescuing miR-185 expression in NSCLC, thereby inhibiting SOX9 expression and the downstream Wnt signaling, and leading to the suppression of NSCLC cell proliferation, invasion and migration, may be a promising strategy for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

The cell migration capability of A549 and SK-MES-1 cells was determined using a cell scratch test. (C) Representative images and (D) statistical analysis are presented. [Corrigedum] miR-185 inhibits non-small cell lung cancer cell proliferation and invasion through targeting of SOX9 and regulation of Wnt signaling A549 and SK-MES-1 cells were transfected with miR-185 mimics or miR-185 inhibitor to achieve ectopic miR-185 expression or miR-185 inhibition. [Extracted from the article]

Objective: To investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice. Methods: A total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD) lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test. Results: The 12-month-old aged mice were divided into a normal gait group (n = 75) and an abnormal gait group (n = 25). Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV) in stride length, two with base of support (BOS) deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was significantly higher in the abnormal gait group as compared to that in the normal gait group (x = 21.986, P < 0.001). All five parameters used to assess gait predicted severe spatial learning and memory impairment in aged mice (P < 0.01). However, the difference of the area under the ROC (receiver operating characteristic) curve for each quantitative gait parameter was not statistically significant. Conclusion: Gait disorders are a predictor of severe spatial learning and memory impairment in aged mice, and stride length, variability of stride length, base of support, cadence, and average speed are all sensitive parameters for assessing gait.

Human adenocarcinomas commonly harbor mutations in the KRAS and MYC proto-oncogenes and the TP53 tumor suppressor gene. All three genetic lesions are potentially pro-angiogenic, as they sustain production of vascular endothelial growth factor (VEGF). Yet Kras-transformed mouse colonocytes lacking p53 formed indolent, poorly vascularized tumors, whereas additional transduction with a Myc-encoding retrovirus promoted vigorous vascularization and growth. In addition, VEGF levels were unaffected by Myc, but enhanced neovascularization correlated with downregulation of anti-angiogenic thrombospondin-1 (Tsp1) and related proteins, such as connective tissue growth factor (CTGF). Both Tsp1 and CTGF are predicted targets for repression by the miR-17-92 microRNA cluster, which was upregulated in colonocytes coexpressing K-Ras and c-Myc. Indeed, miR-17-92 knockdown with antisense 2′-O-methyl oligoribonucleotides partly restored Tsp1 and CTGF expression; in addition, transduction of Ras-only cells with a miR-17-92–encoding retrovirus reduced Tsp1 and CTGF levels. Notably, miR-17-92–transduced cells formed larger, better-perfused tumors. These findings establish a role for microRNAs in non–cell-autonomous Myc-induced tumor phenotypes. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor alpha (TNF-α)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF-α family of death receptor ligands and holds great therapeutic potential as a tumor cell-specific cytotoxic agent. Using a panel of established tumor cell lines and normal cells, we found a significant difference between the number of TRAIL-sensitive cells expressing high levels of c-myc and TRAIL-resistant cells expressing low levels of c-myc (P < 0.05, n = 19). We also found a direct linear correlation between c-myc levels and TRAIL sensitivity in TRAIL-sensitive cell lines (r = 0.94, n = 6). Overexpression of c-myc or activation of a myc-estrogen receptor (ER) fusion sensitized TRAIL-resistant cells to TRAIL. Conversely, small interfering RNA (siRNA)-mediated knockdown of c-myc significantly reduced both c-myc expression and TRAIL-induced apoptosis. The gene encoding the inhibitor of caspase activation, FLICE inhibitory protein (FLIP), appears to be a direct target of c-myc-mediated transcriptional repression. Overexpression of c-myc or activation of myc-estrogen receptor (ER) decreased FLIP levels both in cell culture and in mouse models of c-myc-induced tumorigenesis, while knocking down c-myc using siRNA increased FLIP expression. Chromatin immunoprecipitation and luciferase reporter analyses showed that c-myc binds and represses the human FLIP promoter. c-myc expression enhanced TRAIL-induced caspase 8 cleavage and FLIP cleavage at the death-inducing signaling complex. Combined siRNA-mediated knockdown of FLIP and c-myc resensitized cells to TRAIL. Therefore, c-myc down-regulation of FLIP expression provides a universal mechanism to explain the ability of c-myc to sensitize cells to death receptor stimuli. In addition, identification of c-myc as a major determinant of TRAIL sensitivity provides a potentially important screening tool for identification of TRAIL-sensitive tumors. [ABSTRACT FROM AUTHOR]

The bicistronic microRNA (miRNA) locus miR-144/451 is highly expressed during erythrocyte development, although its physiological roles are poorly understood. We show that miR-144/451 ablation in mice causes mild erythrocyte instability and increased susceptibility to damage after exposure to oxidant drugs. This phenotype is deeply conserved, as miR-451 depletion synergizes with oxidant stress to cause profound anemia in zebrafish embryos. At least some protective activities of miR-451 stem from its ability to directly suppress production of 14-3-3ζ phospho-serine/threonine-binding protein that inhibits nuclear accumulation of transcription factor FoxO3, a positive regulator of erythroid anti-oxidant genes. Thus, in miR-144/451^/^ erythroblasts, 14-3-3ζ accumulates, causing partial relocalization of FoxO3 from nucleus to cytoplasm with dampening of its transcriptional program, including anti-oxidant-encoding genes Cat and Gpx1. Supporting this mechanism, overexpression of 14-3-3ζ in erythroid cells and fibroblasts inhibits nuclear localization and activity of FoxO3. Moreover, shRNA suppression of 14-3-3ζ protects miR-144/451^/^ erythrocytes against peroxide-induced destruction, and restores catalase activity. Our findings define a novel miRNA-regulated pathway that protects erythrocytes against oxidant stress, and, more generally, illustrate how a miRNA can influence gene expression by altering the activity of a key transcription factor. [ABSTRACT FROM AUTHOR]

Abstract Aneuploidy refers to aberrancies in cellular chromosome count, which is prevalent in most human cancers. Chemotherapy is an effective cancer treatment; however, the development of drug resistance is a major concern of conventional chemotherapy. The chemotherapy agent hydroxyurea (HU) targets proliferating cells and has long been applied to treat various human cancers. It remains elusive whether aneuploidy affects the drug sensitivity of hydroxyurea. By generating an inducible aneuploidy model, we found that aneuploid colon cancer cells were resistant to HU treatment compared to euploid controls. Surprisingly, further analyses showed that the HU resistance was dependent on the expression of wild type p53. Activation of the p53 pathway in aneuploidy cells reduced cell proliferation but generated resistance of tumor cells to HU treatment. HU resistance was abrogated in aneuploid cells if p53 was absent but re-gained when inducing proliferation repression in cells by serum deprivation. Our results demonstrate that the HU resistance developed in aneuploid colon cancer cells is mediated by wild type p53 and indicates the prognostic value of combining karyotypic and p53 status in clinical cancer treatment. Graphical abstract fx1 Highlights • Aneuploid colon cancer cells show chemoresistance to hydroxyurea. • Wildtype p53 mediates hydroxyurea resistance in aneuploid colon cancer cells. • Aneuploidy represses cell proliferation via the p53 pathway. • Suppressing cell proliferation by serum starvation generates hydroxyurea resistance. • Karyotype-based stratifying responses to hydroxyurea should be evaluated in clinic. [ABSTRACT FROM AUTHOR]

Highlights • Mice with remote fear memory are sensitive to original and novel reconditioning. • Reconditioning in an original fearful context causes remote fear memory resistance. • Reconditioning in a novel context produces more fear reactions in mice with remote fear memory. • Stress sensitivity of remote fear may be induced by fear memory system consolidation over time. Abstract Exposure of some individuals to recurring traumatic events from the same perpetrator or situation, such as during child abuse or domestic violence, is quite prevalent. Studies have shown that the number of traumatic events experienced is positively related to the severity of post-traumatic stress disorder and other mental disorders. Using a contextual fear conditioning (Cond1) and reconditioning (Cond2) paradigm, which were separated by either 1 or 35 days, we examined fear responses to immediate extinction and retrieval-extinction procedures after repeated fear conditioning stress. Based on the time interval between Cond1 and Cond2, the animals were divided into recent and remote fear memory groups. We observed that when Cond2 was performed in the original conditioning context in which Cond1 was performed, the reconditioned remote fear memory was resistant to the disruptive effect of immediate extinction and retrieval-extinction paradigms. Furthermore, the resistance to disruptive effects could be induced by very low shock intensities, which cannot even induce any fear response in naive animals. When Cond2 was performed in a novel context, animals with remote fear memory acquired a significantly higher fear response to the novel context. Our findings suggest that remote fear memory may be more sensitive to reconditioning and resistant to post-reconditioning disruption. [ABSTRACT FROM AUTHOR]

Post-stroke cognitive impairment (PSCI), commonly seen in the clinical practice, is a major factor impeding patient rehabilitation. Enriched environment (EE) intervention is a simple and effective way to improve cognitive impairment, partially due to the rebalancing of the basal forebrain-hippocampus cholinergic signaling pathway. Epigenetic changes have been identified in many cognitive disorders. However, studies on the effects of EE on epigenetic regulation of cholinergic circuits in PSCI animal models have not yet been reported. In this study, we established a photothrombotic mouse PSCI model and showed that after EE intervention, mice with PSCI had significantly improved water maze performance, better induction of hippocampal long-term potentiation (LTP), enhanced function of the basal forebrain-hippocampus cholinergic circuits of contralateral side of stroke and relatively balanced acetylation homeostasis compared to those of PSCI mice in standard environments (SE). In addition, PSCI mice in EE expressed much higher levels of p-CREB and CBP than in SE, and the chromatins bound to M-type promoter of ChAT gene were more acetylated. These results demonstrate that EE plays an important role in the improvement of PSCI and the underlying mechanism may involve in the acetylation of histones bound to the ChAT gene promoter in cholinergic circuits. [ABSTRACT FROM AUTHOR]

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Summary: The transcription factor GATA-1 is required for terminal erythroid maturation and functions as an activator or repressor depending on gene context. Yet its in vivo site selectivity and ability to distinguish between activated versus repressed genes remain incompletely understood. In this study, we performed GATA-1 ChIP-seq in erythroid cells and compared it to GATA-1-induced gene expression changes. Bound and differentially expressed genes contain a greater number of GATA-binding motifs, a higher frequency of palindromic GATA sites, and closer occupancy to the transcriptional start site versus nondifferentially expressed genes. Moreover, we show that the transcription factor Zbtb7a occupies GATA-1-bound regions of some direct GATA-1 target genes, that the presence of SCL/TAL1 helps distinguish transcriptional activation versus repression, and that polycomb repressive complex 2 (PRC2) is involved in epigenetic silencing of a subset of GATA-1-repressed genes. These data provide insights into GATA-1-mediated gene regulation in vivo. [Copyright &y& Elsevier]

Tectochrysin, a flavonoid compound, can be isolated from propolis, Alpinia oxyphylla Miq , and Lychnophora markgravii. This study evaluated the efficacy of tectochrysin in the treatment of shrimp tropomyosin (ST)-induced mouse asthma. Mice were sensitized with intraperitoneal (i.p.) injection of ST together with aluminum hydroxide as an adjuvant to establish a mouse model of asthma. Mice were i.p.-treated daily with tectochrysin. IgE levels in plasma, Th2 cytokines from both bronchoalveolar lavage (BAL) fluid and splenocytes, and CD200R on basophils in peripheral blood were measured. Histological analyses of lung tissues and accumulation of leukocytes in BAL fluid were performed. Lung eosinophil peroxidase, catalase and glutathione peroxidase activities were examined. ST was found to markedly increase eosinophilic inflammation and Th2 response in mice. Tectochrysin treatment reduced the level of IgE in plasma, the percentage of eosinophils in total white blood cells in peripheral blood, the total number of cells in BAL fluid, and eosinophil peroxidase activity in lung tissues. Tectochrysin attenuated ST-induced infiltration of eosinophils and epithelial mucus secretion in lung tissues and suppressed the overproduction of Th2 cytokines (IL-4 and IL-5) in BAL fluid. Tectochrysin also attenuated Th2 cytokine (IL-4 and IL-5) production from antigen-stimulated murine splenocytes in vitro , decreased the expression of CD200R on basophils in peripheral blood of asthmatic mice and inhibited IL-4 secretion from IgE-sensitized RBL-2H3 cells. In addition, tectochrysin enhanced catalase and glutathione peroxidase activities in lung tissues. Our findings demonstrate that TEC ameliorates allergic airway inflammation by suppressing Th2 response and oxidative stress. [ABSTRACT FROM AUTHOR]