Xie, W., Xie, H., Liu, F., Li, W., Dan, J., Mei, Y., Dan, L., Xiao, X., Li, J. and Chen, X. (2013), Propranolol induces apoptosis of human umbilical vein endothelial cells through downregulation of CD147. British Journal of Dermatology, 168: 739-748. doi: 10.1111/bjd.12193 ...
Dr. Katzmanns Protein Sorting and Receptor Downregulation Lab at Mayo Clinic looks at ESCRTs and associated factors facilitate the MVB sorting process.
(KudoZ) English to Portuguese translation of marked down-regulation: regulação descendente marcante, regulação descendente acentuada [Medical (general) (Medical)].
TY - JOUR. T1 - Tiazofurin down-regulates expression of c-Ki-ras oncogene in a leukemic patient. AU - Weber, G.. AU - Nagai, M.. AU - Natsumeda, Y.. AU - Eble, J. N.. AU - Jayaram, H. N.. AU - Paulik, E.. AU - Zhen, W.. AU - Hoffman, R.. AU - Tricot, G.. PY - 1991/1/1. Y1 - 1991/1/1. UR - http://www.scopus.com/inward/record.url?scp=0025806199&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0025806199&partnerID=8YFLogxK. M3 - Article. C2 - 1705812. AN - SCOPUS:0025806199. VL - 3. SP - 61. EP - 66. JO - Oncology Research. JF - Oncology Research. SN - 0965-0407. IS - 3. ER - ...
In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation) or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous
Oncogenic Ras downregulates CD24 expression in NIH/3T3 cells. CD24 mRNA expression in vector control (Control) and RasV12 cells was determined by (A) RT-PCR and
title: Role of targeting integrin-linked kinase in suppression of invasion and metastasis through downregulation of epithelial to mesenchymal transition in renal cell carcinoma, doi: none, category: Thesis
RESULTS: 775 genes were differentially expressed and clustered in terms of their growth factor responsiveness. As well as identifying uncharacterized genes as novel targets of ErbB2-dependent signalling, ErbB2 overexpression augmented the induction of multiple genes involved in proliferation (e.g. MYC, MAP2K1, MAP2K3), autocrine growth factor signalling (VEGF, PDGF) and adhesion/cytoskeletal regulation (ZYX, THBS1, VCL, CNN3, ITGA2, ITGA3, NEDD9, TAGLN), linking them to the hyper-poliferative and altered adhesive phenotype of the ErbB2-overexpressing cells. We also report ErbB2-dependent down-regulation of multiple interferon-stimulated genes that may permit ErbB2-overexpressing cells to resist the anti-proliferative action of interferons. Finally, IGFBP3 was unique in its pattern of regulation and we further investigated a possible role for IGFBP3 down-regulation in ErbB2-dependent transformation through suppressed IGF1 signalling. We show that IGF1-dependent signalling and proliferation were ...
when a ligan binds, the signal produced by the liogand must be stopped. one way is receptor downregulation, in which the receptor is internalized and degraded in the lysosome ...
I have more to say on some of the ensuing discussion on the direction of causality when I procure some other references, but for now lets fast forward a bit. Taubes goes on to describe metabolic adaptation, regulation and homeostasis. The implication he makes in this discussion is that human metabolism is extremely varied and adaptable. Yes, there are differences due to hormonal levels (e.g. hypothyroidism is a basic example), and different macronutrients elicit different thermogenic effects, but there are limits. Hormonal signals can downregulate metabolism, lower body temp, etc. But theres only so far this can go ... or we die! By the same token, overfeeding studies have demonstrated time and again that whatever signalling and adaptations (futile cycling) may occur in response cannot prevent considerable weight gain. Taubes basically implies that no matter what we may do consciously to (a) maintain caloric balance, (b) induce positive caloric balance, or (c) induce a caloric deficit, our ...
Down-regulation of Akt1 in IGF-IR cells induces migration and EMT. (A, top) The motility of IGF-IR cells with isoform-specific down-regulation of Akt was assess
Oncotarget | https://doi.org/10.18632/oncotarget.1174 Xu Di, Guofeng Zhang, Yaqin Zhang, Kazuyo Takeda, Leslie A. Rivera Rosado, Baolin Zhang
Book now at Article One - American Grill in Washington, explore menu, see photos and read 217 reviews: A very nice atmosphere. We did, however, have to contend with a screaming baby at the front desk. Otherwise, the staff was very polite and attentive.
Our recent work established the essential role of β-arrestin in the internalization of the M2 mAChR [9]. The present study extends the observations of previous work and demonstrates that the agonist-promoted down-regulation of M1 and M2 mAChRs is β-arrestin dependent, and that the ubiquitination pattern of β-arrestin has a critical role in the differential down-regulation for M1 vs M2 mAChRs.. It has been previously established in a variety of cell lines that a prolonged activation of M1 or M2 mAChRs induces receptor down-regulation. In agreement with these findings, long-term stimulation of M1 or M2 mAChRs induced receptor down-regulation with the M1 mAChR showing significantly more down-regulation than M2 subtype. This observation suggests that the two subtypes are differentially regulated by endogenous β-arrestins. No down-regulation of either mAChR subtype occurred in the absence of β-arrestin and either β-arrestin subtype was able to rescue receptor down-regulation.. The observations ...
The disialoganglioside GD3 plays a major role in proliferation, differentiation, and apoptosis. It has been reported that ganglioside GD3 can induce apoptosis through bcl-2 mediated mitochondrial pathway. However, the relationship between ganglioside GD3 and B-cell/CLL lymphoma 2 (Bcl-2) is not full …
In chronic heart failure (HF), sympathetic nervous system overdrive induces the upregulation of G-protein-coupled receptor kinase 2 (GRK2) with a consequent β-adrenergic receptor downregulation/desensitization. Importantly, in failing myocardium, β-adrenergic receptor dysregulation is clinically seen by loss of inotropic reserve. Currently, β-blockers represent a solid "pillar" of HF therapy that at the molecular level efficiently counteracts both β-adrenergic receptor downregulation and GRK2 upregulation. GRK2 inhibition represents a promising new strategy to rescue the failing heart, and we have recently demonstrated that in some animal models, it could be used as a substitute for or in conjunction with β-blockers. GRK2 inhibition may be effective by interfering with other intracellular processes. The present study provides the first evidence of a direct and GRK2-dependent interaction between the β1-adrenergic receptor and the sphingosine-1-phosphate receptor 1 (S1PR1). We show that the ...
This study further elucidates the role of CYP33 in gene transcription by studying the effects of CYP33 overexpression and siRNA-mediated down-regulation on the expression of MLL target genes such as c-MYC, p21, p27, and HOXA9. CYP33 is a cis-trans prolyl isomerase (PPIase) which mediates repression of HOX gene expression after binding to the 3rd PHD finger of MLL through its own RRM domain. Upon binding to MLL, CYP33 increases recruitment of HDAC to the MLL repression domain which in turn leads to deacetylation of histone H3. This ultimately causes repression of MLL target genes (Xia et al. 2003). Chromosomal translocations involving the MLL gene (Mixed Lineage Leukemia) can lead to the production of fusion proteins with any of more than 60 different partner proteins and is implicated in the initiation of leukemia. Expression of MLL fusion proteins leads to increased expression of MLL target genes such as HOXA7, HOXA9 and MEIS1 (Hess et al., 2010). MLL-fusion proteins lack the 3rd PHD finger and ...
Head and thorax development in the Drosophila embryo requires the maternal determinant of the anterior patterning system bicoid (bcd) (Frohnhofer and Nusslein-Volhard, 1986). The Bcd protein is expressed as a maternal anteroposterior concentration gradient in the early developing embryo (Driever and Nusslein-Volhard, 1988b; Struhl et al., 1989) and it is necessary for the expression of numerous zygotic genes in distinct anterior domains. Among them, the gap gene hunchback (hb), which is required for the formation of the segmented part of the head and of the thorax, is activated by low levels of Bcd and expands from 54% to 100% of egg length (EL). In contrast to hb, the expression of another Bcd target gene, the head gap gene orthodenticle (otd), which is involved in the development of antennal and pre-antennal segments, is restricted to 100-70% of EL in the domain where high levels of Bcd concentration are found. Bcd is a homeodomain (HD)-containing transcription factor that probably activates ...
By studying activated DC, it was found that CD82 appeared to have an opposing function to CD37. Whereas CD37 expression was down-regulated following activation of DC, CD82 was up-regulated and restrained DC migration to lymph nodes. DC that were deficient in either CD37 or CD82 were unable to become fully functional and DC that were deficient in CD82 were able to spread much further than CD37 deficient DC. Thus, unactivated DC were observed to have high CD37 expression and low CD82 expression leading to a highly mobile cell that is able to travel easily around the body. Activated DC (DC that have sensed an infection) have low CD37 expression and high CD82 expression which limits mobility of the DC but is able to efficiently signal to immune cells that an infection is present ...
Interferon regulatory aspect (IRF)-3 may have a crucial function in viral and bacterial innate immune system replies by regulating the creation of type We interferon (IFN). cells. This inhibition was because of its suppression from the transcriptional activation TC-E 5001 of IRF-3, as proven by inhibition of IRF-3 PRD (III-I) luciferase activity along with the phosphorylation design of IRF-3 within the immunoblotting test. Furthermore, TQ targeted the autophosphorylation of TANK-binding kinase 1 (TBK1), an upstream essential enzyme in charge of IRF-3 activation. Used together, these results claim that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would eventually decrease the creation of type I IFN. TQ also governed IRF-3, among the inflammatory transcription elements, offering a novel understanding into its anti-inflammatory actions. (TRIF). Upon arousal by LPS, TLR-4 recruits the adaptor proteins TRIF, which in turn recruits tumor necrosis TC-E 5001 aspect ...
Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 1-3. ©2016 AACR.. See related article by Hedayati et al., p. 3310 ...
Sigma-Aldrich offers abstracts and full-text articles by [Fei Gao, Jiyu Guan, Limei Liu, Sheng Zhang, Peipei An, Anran Fan, Guangqi Song, Peng Zhang, Tianchuang Zhao, Bo Tang, Xueming Zhang, Ziyi Li].
Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.
In the original manuscript, the text in figure 1 is illegible. Furthermore, there is an unnecessary carriage return (page 1716, ~line 18) crystallographic ... methods. [...]
Curcumin blocks CCL2 induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity is an eagle-i resource of type Journal article at Oregon Health & Science University.
Mutations in the parkin gene, which encodes a ubiquitin ligase, has been implicated as one of causative factor for genetic parkinsonism. Interestingly, parkin role has also been implicated in cancer as a putative tumor suppressor with the gene been frequently targeted by deletion and inactivation in several human malignant tumors. Here, we demonstrated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells and that the restoration of parkin expression promoted G1 phase cell-cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Furthermore, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin-null mouse model exhibited increased levels of cyclin D1, VEGF receptor, and Akt phosphorylation, and divided significantly ...
Conversely, if one supposes that internalized receptor is immune to down-regulation and that down-regulation occurs proportionately to occupancy of receptor by agonist in the membrane, then again, down-regulation is greater at low fenoterol concentrations than the model predicts. As before this proposal cannot be saved by supposing a saturable process because the down-regulation is a first order process.. Kinetic models that are consistent with the data can be constructed if a pool of receptor in addition to the endocytosed pool can be invoked. Here we propose a scheme (Fig. 7A, model II), the key features of which are that down-regulation can occur by either of two pathways; one pathway involving a high agonist affinity component with a low capacity that is independent of internalization and a second pathway using a low-affinity, high-capacity event that is closely correlated with internalization. This scheme provides an explanation for the dissociation of internalization from down-regulation ...
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Wei, W.,Ming, X.,Yi, Z. Y.,et al. Autoimmunity Mediated Down-regulation Of B 2-adrenergic Receptor In COPD[J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE,2010,181 ...
This morning I had my Down Regulation appointment. This consisted of yet another internal scan. And being taught how to use the pen that holds my next lot of drugs. Somehow I get the feeling that sticking a needle in me is a whole lot different to sticking a needle into the little pad thing…
Mouse monoclonal antibody MX35 was developed against ovarian cancer. The antibody showed homogeneous reactivity with approximately 90% of human ovarian epithelial cancers and with a limited number of normal tissues by immunohistochemistry. Although mAb MX35 has been used in a number of clinical trials in ovarian cancer, it has been difficult to define the molecular identity of MX35. We report here that mAb MX35 recognizes the sodium-dependent phosphate transport protein 2b (NaPi2b) in human cancer cells. This conclusion is based on several lines of experimental evidence, including 1) the identification of SLC34A2, the gene coding for NaPi2b, by immunoscreening an ovarian cancer cell line cDNA expression library with mAb MX35; 2) mass spectrometry sequencing of peptides obtained by fragmentation from mAb MX35 affinity-purified antigen, which show complete sequence homology to amino acid sequences in NaPi2b; 3) selective down-regulation of SLC34A2 gene expression by RNA interference and the ...
miRNAs (microRNAs) have been shown to play a role in myocardial fibrosis. The present study was designed to analyse whether alterations in miRNA expression contribute to the progression of myocardial fibrosis in AS (aortic valve stenosis) patients through up-regulation of the pro-fibrotic factor TGF-β1 (transforming growth factor-β type 1). Endomyocardial biopsies were obtained from 28 patients with severe AS, and from the necropsies of 10 control subjects. AS patients presented increased myocardial CVF (collagen volume fraction) and TGF-β1 compared with the controls, these parameters being correlated in all patients. Patients were divided into two groups by cluster analysis according to their CVF: SF (severe fibrosis; CVF ,15%; n=15) and non-SF (CVF ≤15%; n=13). TGF-β1 was increased in patients with SF compared with those with non-SF. To analyse the involvement of miRNAs in SF, the miRNA expression profile of 10 patients (four with non-SF and six with SF) was analysed showing that 99 ...
No effective chemotherapy for the treatment of malignant brain tumors, especially glioblastoma, exists so far. Despite the progress in surgical techniques and advances in the irradiation treatment, the concomitant chemotherapy is essential for the prevention of relapse and of major importance for patient outcome. The introduction of temozolomide combined with radiation in clinical practice led to slightly improved long-term survival, but malignant gliomas remain resistant to cancer chemotherapy. Thus, new strategies for the treatment of brain tumors are still needed. Objectives of this work were the evaluation of the TmHU protein as siRNA transfection reagent (Chapter 2), investigations on new kinesin Eg5 inhibitors, which specifically inhibit cell division during mitosis (Chapter 3), and the exploration of new tariquidar analogs as ABCB1 and ABCG2 inhibitors (Chapter 4). Due to the selective down-regulation of oncogene expression by small interfering RNA, siRNAs are considered as promising ...
Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is
TY - JOUR. T1 - CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells. AU - Yoo, Young Do. AU - Park, Jong Kuk. AU - Choi, Ju Youn. AU - Lee, Kee Ho. AU - Kang, Yoon Koo. AU - Kim, Chong Suk. AU - Shin, Sang Won. AU - Kim, Yeul Hong. AU - Kim, Jun Suk. PY - 1998. Y1 - 1998. N2 - Paclitaxel induces a cell cycle block at G2-M phase by preventing the depolymerization of microtubules and induces p53-independent apoptosis in many cancer cells. We observed that gastric cancer cells treated with paclitaxel have shown a cyclin-dependent kinase (CDK)4 down-regulation. This paclitaxel-induced CDK4 down-regulation resulted in a cell cycle arrest at G1-S phase. To confirm this observation, we prepared stable transfectants that overexpressed CDK4 and analyzed the cell cycle progression. Ectopic expression of CDK4 in SNU cells resulted in a release of paclitaxel-induced G1 arrest. The release of G1 arrest by enforced expression of CDK4 seems to make the cells more ...
Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin.[citation needed] Like other physically addictive drugs, nicotine withdrawal causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. As dopamine regulates the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. An example is the increase in norepinephrine, one of the successors to dopamine, which inhibit reuptake of the glutamate receptors,[45] in charge of memory ...
Over the past few years, the discovery of miRNAs has changed the landscape of human genetics and they have been widely studied in the field of oncology, where altered miRNA expression has been observed in a variety of human cancers [28]. Indeed, miRNA-expression profiling of human epithelial malignancies has led to the identification of signatures associated with diagnosis, staging, progression, prognosis and even response to treatment [29, 30]. However, few mechanistic studies have been carried out to dissect the functional role of miRNA in RCC, particularly in the context of "immune dysfunction" which may underlie disease progression. In fact, attaining effective tumor immunity is a major goal of the modern biologic therapy, limited by the tumor microenvironment and regulatory mechanisms affecting T cell and NK cell effectors [31].. The major finding in this report is that CD8+ T cells isolated from RCC patients exhibit defects in proliferation and a propensity to undergo apoptotic cell death ...
Research on the regulation of fish muscle physiology and growth was addressed originally by classical in vivo approaches; however, systemic interactions resulted in many questions that could be better considered through in vitro myocyte studies. The first paper published by our group in this field was with Tom Moon on brown trout cardiomyocytes, where the insulin and IGF-I receptors were characterized and the down-regulatory effects of an excess of peptides demonstrated. We followed the research on cultured skeletal muscle cells through the collaboration with INRA focused on the characterization of IGF-I receptors and its signaling pathways through in vitro development. Later on, we showed the important metabolic role of IGFs, although these studies were only the first stage of a prolific area of work that has offered a useful tool to advance in our knowledge of the endocrine and nutritional regulation of fish growth and metabolism. Obviously, the findings obtained in vitro serve the purpose to ...
The central dogma postulates that genes are first copied into messenger RNAs, which are then decoded into proteins with the help of transfer RNAs and ribosomal RNAs. It has long been known that there is more to the world of RNA than just these three classes, but the development of high-throughput RNA sequencing has revealed just how active RNAs can be. Much of the genome is transcribed, without these transcripts being translated into proteins. As these non-coding RNAs have been characterized, it is clear that many of them have regulatory roles. It has also been revealed how chemical modifications to all classes of RNAs affect their behavior, such as what they interact with and when, and how long they hang around for before being degraded.. Genome Biology has recently published a special issue on RNA & gene regulation, exploring this new world.. Perhaps some of the best understood regulatory RNAs are the microRNAs, short RNAs that bind to mRNA which mostly causes downregulation by either ...
Tryndyak, V. P., Ross, S. A., Beland, F. A. and Pogribny, I. P. (2009), Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet. Mol. Carcinog., 48: 479-487. doi: 10.1002/mc.20484 ...
PIK-93 is a potent PI3K inhibitor. PIK93 selectively inhibits the type III PI 4-kinase beta enzyme, and small interfering RNA-mediated down-regulation of the individual PI 4-kinase enzymes, revealed that PI 4-kinase beta has a dominant role in ceramide transport between the ER and Golgi.
Our results show that genetic elimination of BAMBI as a modulator of the signaling of the family of TGF cytokines renders the almost-resistant C57BL/6 mouse strain more susceptible to the development of diabetic glomerular abnormalities, as determined by proteinuria with a widening of the FPs. This is associated with increased activation of ERK1/2 and Smad1/5 alternative TGF-β signaling pathways. The Vegfr2 and Angpt1 genes, which control glomerular endothelial survival and microvascular stability, were downmodulated in glomeruli from diabetic BAMBI−/− mice compared with BAMBI+/+ mice. Incubation of glomeruli from nondiabetic BAMBI+/+ or BAMBI−/− mice with TGF-β resulted in further downregulation of Angpt1 and Vegfr2 in glomeruli from BAMBI−/− compared with BAMBI+/+ mice. The enhanced downregulation of Vegfr2 in glomeruli of diabetic mice by eliminating BAMBI could be localized to glomerular endothelial cells using an H2B-EYFP reporter under the control of Vegfr2/Flk1 regulatory ...
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TY - JOUR. T1 - Copper Depletion Down-regulates Expression of the Alzheimers Disease Amyloid-β Precursor Protein Gene. AU - Bellingham, Shayne A.. AU - Lahiri, Debomoy K.. AU - Maloney, Bryan. AU - La Fontaine, Sharon. AU - Multhaup, Gerd. AU - Camakaris, James. PY - 2004/5/7. Y1 - 2004/5/7. N2 - Alzheimers disease is characterized by the accumulation of amyloid-β peptide, which is cleaved from the amyloid-β precursor protein (APP). Reduction in levels of the potentially toxic amyloid-β has emerged as one of the most important therapeutic goals in Alzheimers disease. Key targets for this goal are factors that affect the regulation of the APP gene. Recent in vivo and in vitro studies have illustrated the importance of copper in Alzheimers disease neuropathogenesis and suggested a role for APP and amyloid-β in copper homeostasis. We hypothesized that metals and in particular copper might alter APP gene expression. To test the hypothesis, we utilized human fibroblasts overexpressing the ...
In the present study, we demonstrate a novel mechanism that causes down-regulation of TβRII. This mechanism involves the binding of an Sp1-HDAC1 complex to a specific Sp1 site of the TβRII promoter in PDAC cells. Treatment of BxPC-3 and MIA PaCa-2 cells with a HDAC inhibitor, TSA, strongly activates TβRII promoter and induces TβRII expression. An increase in the association of TβRII promoter chromatin with acetylated histone H4 was observed after TSA treatment. These findings suggest that histone deacetylation plays a role in repression of the TβRII gene in PDAC. Luciferase reporter assays using serial deletion constructs revealed that a major TSA response region is located within the NRE-2 (−100 to −67) region of the TβRII promoter. Analysis using site-specific mutation constructs demonstrated that a specific Sp1 site (Sp1C) and an inverted CCAAT element located at −102 and −83 bp relative to the transcription start site of TβRII promoter are required for TSA-mediated reversal ...
TY - JOUR. T1 - Potent suppression of HIV type 1 infection by a short hairpin anti-CXCR4 siRNA. AU - Anderson, Joseph S. AU - Banerjea, Akhil. AU - Planelles, Vicente. AU - Akkina, Ramesh. PY - 2003/8/1. Y1 - 2003/8/1. N2 - The phenomenon of RNA interference (RNAi) sparked a new surge in the area of posttranscriptional gene silencing methodologies and their potential application for HIV-1 gene therapy. A potentially promising strategy is to exploit siRNAs to prevent viral entry at the cell surface by down-regulating essential cell surface HIV-1 coreceptors. In the present studies we targeted the CXCR4 coreceptor for disruption with siRNA to inhibit HIV-1 entry as a first step toward the ultimate goal of translating this to gene therapy for AIDS. A stem-loop hairpin structured anti-CXCR4 siRNA was designed and synthesized in vitro by transcription with T7 polymerase. Down-regulation of the coreceptor was assayed in U373-Magi-CXCR4 cells. FACS analysis showed marked down-regulation of CXCR4 on the ...
Statins have action mechanisms that may work nicely in preventing recurrence during acute stage of infarction!. First, statins have antithrombotic effects and lower thrombogenicity. Statins prolong time to arterial thrombosis in endothelial injury model, inhibit P-selectin expression and platelet aggregation, reduce platelet PAR-1 thrombin receptor, and reduce tissue factor levels in plasma, its expression on monocyte surface, and atherosclerotic plaques. Second, statins enhance thrombolysis. They reduce PAI-1, increase t-PA activity and reduce fibrinogen level. Combined treatment of statins and t-PA in rats reduces the infarct size and downregulates expression of tissue factor, ICAM-1, vWF, and MMP-9. In addition, t-PA induced toxicity is reversed by statins.. Third, statins have anti-inflammatory actions that can stabilize and even regress plaques. Statins reduce the number of T-lymphocytes within plaques, inhibit migration and activation of monocyte/macrophage system, and reduce matrix ...
Systemic loss of one IL-6 cytokine member exhibits mild or unexpected morphological vascular phenotypes (19), e.g., systemic deletion of IL-6 in a mouse model prone to atherosclerosis elicits detrimental effects on atherosclerotic plaque development, potentially via an IL-6−dependent down-regulation of its counteracting cytokine IL-10 (20). The complete systemic gp130 knockout, in contrast, shows profound defects in cardiac and hematopoetic development, resulting in premature death in utero or soon after birth. Thus, to delineate the role of the hepatic APR in atherosclerosis, we selectively deleted the gp130 receptor in hepatocytes using the Cre-loxP system. The genetic modification was confirmed by a PCR reaction demonstrating the gene inactivation exclusively in liver, but not in heart, aorta, or spleen, and by functional analysis of gp130-dependent, LIF-induced STAT3 phosphorylation and SAA release from hepatocytes from controls, but not from gp130− mice. Thus, the introduction of loxP ...
FOXO3, also known as FOXO3a (and previously as FKHRL1), is a Forkhead protein of the O subclass. FOXOs have overlapping expression profiles and activities, but FOXO3a is known to be particularly important in cell cycle control and apoptosis, the immune system, fertility, and longevity [1][2][3]. It has a widespread distribution in the body, although expression levels are not equal throughout tissues. It contains a characteristic Forkhead box DNA binding domain, and is able to up- and downregulate expression of a variety of genes via binding of its consensus Forkhead Recognition Element, or similar sequences (including Insulin Response Elements). DNA recognition is performed by helix 3 of the DBD, although other parts of the DBD also contact the DNA to increase binding stability. FOXO3 is a human orthologue of C. eleganss daf-16, a gene required for the long-lived phenotype of daf-2-null nematodes. FOXO3s involvement in longevity, aging and senescence may be linked to its roles in oxidative ...
The addition of high-dose cytarabine to the treatment of mantle cell lymphoma (MCL) has significantly prolonged survival of patients, but relapses are common and are normally associated with increased resistance. To elucidate the mechanisms responsible for cytarabine resistance, and to create a tool for drug discovery investigations, we established a unique and molecularly reproducible cytarabine resistant model from the Z138 MCL cell line. Effects of different substances on cytarabine-sensitive and resistant cells were evaluated by assessment of cell proliferation using [methyl-14C]-thymidine incorporation and molecular changes were investigated by protein and gene expression analyses. Gene expression profiling revealed that major transcriptional changes occur during the initial phase of adaptation to cellular growth in cytarabine containing media, and only few key genes, including SPIB, are deregulated upon the later development of resistance. Resistance was shown to be mediated by down-regulation of
Down-regulation of apoptosis genes has been implicated in the development and progression of malignant melanoma. We used cDNA microarray to evaluate pro-apoptotic gene expression comparing normal skin
Cell surface glycoprotein CD200 receptor 1 is a protein that in humans is encoded by the CD200R1 gene. This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner. Alternative splicing of this gene results in multiple transcript variants. GRCh38: Ensembl release 89: ENSG00000163606 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000022667 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, Barclay AN (Sep 2000). "Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in ...
N|sup|6|/sup|-Methyladenosine (m6A) is the most prevalent internal modification that occurs in the mRNA of eukaryotes and plays a vital role in the post-transcriptional regulation. Recent studies highlighted the biological significance of m6A modification in the nervous system, and its dysregulation …
Chronic exposure of various cell types to adrenergic agonists leads to a decrease in cell surface beta 2-adrenergic receptor (beta 2AR) number. Sequestration of the receptor away from the cell surface as well as a down-regulation ...
These effects are mediated by nuclear accumulation of the p27(Kip1) inhibitor induced by the downregulation of the p45(Skp2) and Cks1 proteins, which target p27(Kip1) for degradation ...
A liquid crystal device includes a pair of transparent substrates disposed with a prescribed gap therebetween and each having a transparent electrode thereon, a photoelectric conversion semiconductor layer not subjected to rubbing formed on one of the pair of transparent substrates, and alignment film subjected to rubbing formed on the other of the pair of transparent substrates, an a liquid crystal disposed between the photoelectric conversion semiconductor layer and the alignment film. As the photoelectric conversion semiconductor is freed from an aligning performance, the material thereof is freed from the constraint and can be selected so as to optimize the photoelectric conversion performance.
We have reported recently that sodium butyrate suppressed IFN-γ, but not the LPS-mediated induction of nitric oxide and TNF-α in microglia via the specific inhibition of NF-κB. In order to further determine the upstream signaling mechanism involved in the IFN-γ-specific down-regulation of iNOS by sodium butyrate in microglia, this study investigated the effect of sodium butyrate on the MAP kinase activities. Sodium butyrate significantly repressed the phosphorylation of ERK induced by IFN-γ, but had little effect on that induced by LPS. This suggests that sodium butyrate suppresses the IFN-γ-induced iNOS expression by inhibiting the ERK to NF-κB pathway. In addition, it was found that sodium butyrate suppressed the IFN-γ-induced interferon regulatory factor 1 (IRF-1) expression via the inhibition of ERK. Therefore, the ERK signaling pathway appears to play a key role in the sodium butyrate-mediated down-regulation of iNOS in the IFN-γ-stimulated microglia. © 2005 Elsevier B.V. All ...
Mycobacterium tuberculosis (Mtb) causes death of 2-3 million people every year. The persistence of the pathogenic mycobacteria inside the macrophage occurs through modulation of host cell signaling which allows them, unlike the other non-pathogenic species, to survive inside the host. The secretory proteins of M. tuberculosis have gained attention in recent years both as vaccine candidates and diagnostic tools; they target the immune system and trigger a putatively protective response; however, they may also be involved in the clinical symptoms of the disease. Our studies showed that RD-1-encoded secretory protein ESAT-6 is involved in modulation of the mitogen-activated protein (MAP) kinase-signaling pathway inside the macrophage. ESAT-6 induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the cytoplasm but not in the nucleus, which normally is the case for MAP kinases. ESAT-6 also antagonized LPS-induced ERK1/2 phosphorylation in the nucleus. Stimulation of cells by ESAT-6
AIM: To investigate whether Tg737 is regulated by microRNA-548a-5p (miR-548a-5p) and correlates with hepatocellular carcinoma (HCC) cell proliferation and apoptosis. was evaluated by flow cytometry. RESULTS: Down-regulation of Tg737 which is a target gene of miR-548a-5p accelerated HCC cell proliferation and miR-548a-5p promoted HCC cell proliferation and and and < 0.05. RESULTS Down-regulation of Tg737 promotes HCC cell proliferation in vitro To illuminate the role of Tg737 in HCC cell proliferation HCC cell lines HepG2 and MHCC97H were transfected with a si-Tg737 sequence or negative control (Figure ?(Figure1A).1A). Down-regulation of Tg737 significantly promoted the proliferation of HepG2 and MHCC97H cells and enhanced colony forming capability (Figure ?(Figure1B1B and C). The distribution JTC-801 of HepG2 and MHCC97H cell cycles showed that the percentage of cells in G0/G1 phase significantly decreased in Tg737 down-regulated cells compared with their counterparts while the cells in S phase ...
AR plays an important role in the development of prostate cancer as well as in the transition to castration-resistant state, which is highly aggressive and resistant to chemotherapy (4, 38). Thus, the preclinical/clinical development of novel agents that are safe but can suppress AR signaling is highly desirable. The present study shows that DATS treatment suppresses protein level of AR in both LNCaP cells and their androgen-independent variant. The DATS-mediated AR protein down-regulation is maintained for at least up to 24 hours even after removal of the drug. In addition, DATS treatment exhibits significant antiproliferative effect against androgen-stimulated growth of LNCaP cells.. We also conclude that the DATS-mediated suppression of AR protein level leads to inhibition of transcriptional activity of AR as evidenced by a significant decrease in secreted as well as intracellular levels of PSA in both LNCaP and C4-2 cells. Structure-activity analysis reveals that even a subtle change in the ...
In ,ralph.1146355927D at news.arizona.edu,, ralph at ccit.arizona.edu (Ralph M Bernstein) writes: ,chan wrote: , ,,In article ,3kolh2$b8k at styx.uwa.edu.au, Alec Redwood, ,,aredwood at uniwa.uwa.edu.au writes: ,,,: Can anyone tell me about TH3 cells and/or direct me to an article. ,, ,, ,,These cells were coined by those working in EAE model. They found high ,,TGFb producers when fed MBF orally. The cells did not fit into neat TH1 ,,or TH2 so they coined the term. I think this is bunk. There is no clear ,,Th1 or Th2 anyway. These cells are far more versatile than those in , ^^^^^^^^^^ , ,,Huh?!? , ,,CD4+ TH1 cells have decidedly different cytokine production than CD4+TH2 ,,cells. There is evidence that one cell type can downregulate the other ,,cell type (or phenotype, if you think they are the same cell). However, ,,its interesting to note that Fas Ligand-mediated cytoxicity/apoptosis is ,,mediated by TH1 CD4+ cells and not the TH2 CD4+ cells (This doesnt ,,exclude the CD8+ cells from ...
Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis., 2016 ...
The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers. ...
Chen, G.; Peng, J.; Zhu, W.; Tao, G.; Song, Y.; Zhou, X.; Wang, W., 2015: Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy
The system for this is not recognized but could be triggering crucial generic pathways that suppress the proliferation of T. gondii. A latest review, using
زمینه و هدف: عوامل miR-133وSRF در فرآیندهای مختلف سلولی درگیر می باشند، اما هنوز تأثیر تمرین استقامتی بر بیان آنها در عضلات تند و کند انقباض مشخص نشده است. هدف این تحقیق ارزیابی تاثیر تمرین استقامتی بر بیان miR-133 و SRF عضلات تند و کند انقباض در رت‌های نر نژاد ویستار بود. روش تحقیق: در این مطالعه 14 رت با وزن 20±113 گرم (5 هفته سن داشتند) به مدت 4 هفته تحت شرایط کنترل شده، نگهداری شدند و بعد از دوره آشناسازی به صورت تصادفی به دو گروه کنترل و تجربی (7 سر رت در هر گروه) تقسیم شدند. گروه تجربی یک برنامه تمرین استقامتی 14 هفته ای، هفته ای 6 جلسه (که بتدریج به 60 دقیقه و سرعت 30 متر بر
Glutathione, present in low millimolar concentrations in most cells, constitutes the chief water-soluble intracellular oxidant scavenger, protecting the membranes, DNA and proteins of oxidatively stressed tissues. (Ascorbate is likewise of importance in this regard.) It also opposes the proinflammatory/proapoptotic signalling effects of hydrogen peroxide, both by enabling the degradation of this compound via glutathione peroxidase and by working with glutaredoxin to promote the restoration of sulfenic acids to sulfhydryl form.36-40 As we have seen, it can also oppose IL-1β-induced inflammation via its inhibitory impact on NSMase-2. A further role of glutathione is to aid excretion of relatively hydrophobic compounds via conjugation reactions catalysed by glutathione-S-transferases.41. Intracellular cysteine availability is rate limiting for glutathione synthesis, such that increased cysteine levels boost this synthesis.42 N-acetylcysteine (NAC) is a venerable nutraceutical which acts as a ...
Background: A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8(+) T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings: In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any ...
Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further
Cytokines are thought to cause the depression of cytochrome P-450 (CYP)-associated drug metabolism in humans during inflammation and infection. We have examined the role of five cytokines, i.e., interleukin-1 beta, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, on the expression of CYP1A2, CYP2C, CYP2E1, CYP3A, and epoxide hydrolase in primary human hepatocyte cultures. Steady state P-450 and epoxide hydrolase mRNA levels, as well as ethoxyresorufin-O-deethylase and nifedipine oxidation activities, which are mainly supported by CYP1A1/1A2 and CYP3A, respectively, were measured. Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha were found to be the most potent depressors of P-450 enzymes. After 3 days of treatment, both mRNA levels and enzyme activities were depressed, typically by at least 40%, whatever the cytokine and the enzyme considered. Interferon-gamma also suppressed CYP1A2 and CYP2E1 mRNA levels and ethoxyresorufin-O-deethylase activity ...
MicroRNA-200c (miR-200c) is one of the short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. It also acts as considerable modulator in the process of epithelial-to-mesenchymal transition (EMT), a cell development regulating process that affects tumor development and metastasis. However, the role of miR-200c in bladder cancer cells and its mechanism has not been well studied. The purpose of this study was to determine the potential role of miR-200c in regulating EMT and how it contributed to bladder cancer cells in invasion, migration and proliferation. Real-time reverse transcription-PCR was used to identify and validate the differential expression of MiR-200c involved in EMT in 4 bladder cancer cell lines and clinical specimens. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200c was over-expressed in UMUC-3 and T24 cells using a lentivirus construct, respectively. Protein expression and signaling pathway
The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or M1 phenotype. Conversely, stimulation of
Background Thymoma and thymic carcinoma will be the most frequent subtypes of thymic epithelial tumors (TETs). Carcinoma (TC1889) cell collection. Epigenetic transcriptional legislation of miR-145-5p was analyzed by dealing with the TC1889 cell series using the HDAC inhibitor Valproic Acidity (VPA). Results Beginning with the identification of the 69-gene personal of miR-145-5p putative focus on mRNAs, whose appearance was correlated compared to that of miR-145-5p inversely, the expression was accompanied by us of a few of them in vitro upon overexpression of miR-145-5p; we observed that led to the down-regulation of the mark genes, impacting on TETs cancerous phenotype. We also discovered that VPA treatment of TC1889 cells resulted in miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p focus on genes and exhibited antitumor results, as indicated with the induction of cell routine arrest and by the reduced amount of cell viability, colony forming migration and capability ...
PRIMARY OBJECTIVES:. I. To assess the activity of A6, as measured by the 6-month progression-free survival (PFS) rate and objective tumor response (complete or partial) rate, in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma.. II. To determine the frequency and severity of adverse events as assessed by CTCAE v3.0.. SECONDARY OBJECTIVES:. I. To characterize the duration of PFS and overall survival. II. To identify biomarkers of drug effect on peripheral blood mononuclear cells (PBMCs).. TERTIARY OBJECTIVES:. I. To explore whether genes identified as being up- or down-regulated by exposure of human PBMCs to A6 in vitro are also up- or down-regulated following treatment of patients with A6 in vivo.. II. To explore whether there is an association between the expression of candidate A6 receptors in the tumor prior to treatment with A6 (as determined by IHC) and response and PFS.. III. To explore whether there is an association between change ...
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene. The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. TRIM22 is also a target gene of the tumor suppressor protein p53. TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore, TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase. The protein down-regulates transcription from the HIV-1 long terminal repeat promoter region, suggesting that function of this protein may be to mediate interferons antiviral effects. Other proteins that function to restrict HIV replication include TRIM5alpha and APOBEC3G. It has been demonstrated that ...
The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebral meninges and specific downregulation of Tek/Tie-2, the receptor for angiopoietin-1. We also show that dysmegakaryopoiesis in Fli-1 null embryos resembles that frequently seen in patients with terminal deletions of 11q (Jacobsen or Paris-Trousseau Syndrome). We map the megakaryocytic defects in 14 Jacobsen patients to a minimal region on 11q that includes the Fli-1 gene and suggest that dysmegakaryopoiesis in these patients may be caused by hemizygous loss of Fli-1 ...
Manni I., Tunici P., Cirenei N., Albarosa R., Colombo B.M., Roz L., Sacchi A., Piaggio G., Finocchiaro G.. Mxi1 is a Mad family member that plays a role in cell proliferation and differentiation. To test the role of Mxi1 on tumorigenesis of glioma cells we transfected a CMV-driven MXI1 cDNA in U87 human glioblastoma cells. Two clones were isolated expressing MXI1 levels 18- and 3.5-fold higher than wild-type U87 cells (clone U87.Mxi1.14 and U87.Mxi1.22, respectively). In vivo, U87.Mxi1.14 cells were not tumorigenic in nude mice and delayed development of tumours was observed with U87.Mxi1.22 cells. In vitro, the proliferation rate was partially and strongly inhibited in U87.Mxi1.22 and U87.Mxi1.14 cells respectively. The cell cycle analysis revealed a relevant accumulation of U87.Mxi1.14 cells in the G(2)/M phase. Interestingly, the expression of cyclin B1 was inhibited to about 60% in U87.Mxi1.14 cells. This inhibition occurs at the transcriptional level and depends, at least in part, on the ...
TY - JOUR. T1 - Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma. AU - Kim, Hyun Soo. AU - Yoon, Gun. AU - Do, Sung Im. AU - Kim, Sung Joo. AU - Kim, Youn Wha. PY - 2016/3/22. Y1 - 2016/3/22. N2 - A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and ...
Specific metabolic programs are activated by immune cells to fulfill their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis. They acquire exogenous fatty acids and store lipids in droplet form. Autophagy is differentially activated in B1a B cells, and deletion of the autophagy gene Atg7 leads to a selective loss of B1a B cells caused by a failure of self-renewal. Autophagy-deficient B1a B cells down-regulate critical metabolic genes and accumulate dysfunctional mitochondria. B1 B cells, therefore, have evolved a distinct metabolism adapted to their residence and
Purpose : Activation of the Epidermal Growth Factor Receptor (EGFR) is critical in corneal epithelial regeneration and homeostasis. The clinical use of EGFR ligands (e.g. epidermal growth factor - EGF) are not reliable tools to restore and maintain the epithelial layer, likely due to high endogenous EGF levels and intrinsic mechanisms of receptor down-regulation. One mediator of EGFR down-regulation is the E3 ubiquitin ligase, c-Cbl. Ubiquitylation of the EGFR targets it for lysosomal degradation; using RNAi to attenuate c-Cbl expression enhanced the kinetics of corneal epithelial wound healing. We postulate that supplementing the relatively high, endogenous levels of EGF (~2-3 ng/ml) in human tears with a c-Cbl antagonist will prevent EGFR down-regulation and enhance receptor activity and promote homeostasis of the epithelial layer. In this study, we identify and test potential c-Cbl antagonist for binding and inhibitory activity ...
Durham, NC - Alejandro Aballay, PhD, Professor in the Department of Molecular Genetics and Microbiology and Director of the Center for Host Microbial Interactions at Duke University, will be receiving an NIH MERIT Award from NIGMS for his research project on the role of the nervous system in controlling immunity in the model host C. elegans.. Dr. Aballays project will be a multidisciplinary research program regarding the study of neural circuits involved in the control of stress responses and innate immunity. Recent studies from his laboratory indicate that different immune mechanisms are controlled at the organismal level by the nervous system. His laboratory has demonstrated that specific neurons suppress innate immunity in the intestinal cells of the nematode Caenorhabditis elegans, in part by down-modulating a mitogen-activated protein kinase signaling pathway similar to the mammalian p38 MAPK pathway that is highly conserved across metazoans. They found that NPR-1, a G-protein coupled ...
Abstract. A phase III clinical trial showed gemcitabine chemotherapy combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib significantly improved overall survival in patients with advanced pancreatic cancer. Therefore, we studied whether addition of gemcitabine to erlotinib in cancer cells having intrinsic or acquired erlotinib resistance could restore chemosensitization in these cells. We studied the synergistic effect of erlotinib and gemcitabine in EGFR-overexpressing A-431 cells with acquired erlotinib resistance and in intrinsic erlotinib-resistant triple negative breast cancer (TNBC) BT-549, MDA-MB-231 and MDA-MB-468 cell lines. Erlotinib and gemcitabine were synergistic in both parental intrinsically erlotinib-sensitive A-431 cells (combination index = 0.69 at the effective dose [ED50]) and in two A-431 cell pools that had acquired erlotinib resistance (combination indices = 0.63 and 0.49 at ED50). The synergistic effect of erlotinib and gemcitabine on ...
Amphetamine has complex behavioral actions in the rat that depend upon the release of dopamine in striatal and mesolimbic brain regions. To explore a possible role of the dopamine-sensitive cAMP second-messenger system in mediating these effects, we examined the effects of in vivo amphetamine treatments on the D1 receptor-coupled adenylate cyclase system in membranes from striatal and mesolimbic rat brain regions. The results show that amphetamine produces a regional, dose- and time- dependent down-regulation of adenylate cyclase activity. Intermediate and high doses of amphetamine (2.5 and 7.5 mg/kg, respectively), but not a low dose (1.0 mg/kg), resulted in a decrease in the apparent Vmax and/or an increase in the apparent Ka for the selective D1 partial agonist, SKF38393, in striatal membranes 30 min after amphetamine treatment. Treatment of rats with 7.5 mg/kg amphetamine for 30 and 60 min, but not 10 min, similarly resulted in a down-regulation of D1- mediated adenylate cyclase activity in ...
Vertebrate neurogenesis involves sequential actions of transcription factors. neurogenins, encoding Atonal-related bHLH transcription factors, function as neuronal determination genes in Xenopus. neurogenins and antother bHLH factor gene, Mash1, are expressed in distinct subsets or areas of cells giving rise to neurons, suggesting that these genes play important roles to generate distinct populations of neurons. A mammalian homologue of BarH (MBH1) is expressed in a complementary pattern to Mash1 expression in the developing nervous system like neurogenins. Forced expression of MBH1 down-regulates expression of Mash1 and up-regulates neurogenin2/Math4A, a member of neurogenins, in P19 cells during neuronal differentiation. This suggests that MBH1 is a potential regulator of mammalian neural bHLH genes, thereby establishing distinct pathways of neuronal differentiation ...
Some of us may remember conferences with sessions entitled Why 3D? Such sessions are a thing of the past now because there is an accumulating body of evidence - joined by the recent article from Leslie and colleagues [1] - demonstrating the importance and utility of 3D culture systems to discover and model biological process with in vivo relevance. For example, when normal and malignant human breast cells are placed in 3D cultures of laminin-rich gels, the former cells form growth-arrested, lumen-containing acini and the latter cells form disorganized structures [2]. Inhibitors of epidermal growth factor receptor and β1-integrin can revert the malignant phenotype, and each inhibitor downmodulates its own target as well as the other targets only in 3D but not in cells grown as monolayer cultures - suggesting that signaling pathways reciprocally regulate each other to maintain the transformed state [3]. ErbB2/HER2-induced transformation of 3D structures, but not cell proliferation, requires ...
Mancini A, Koch A, Wilms R, Tamura T (April 2002). "c-Cbl associates directly with the C-terminal tail of the receptor for the macrophage colony-stimulating factor, c-Fms, and down-modulates this receptor but not the viral oncogene v-Fms". J. Biol. Chem. 277 (17): 14635-40. PMID 11847211. doi:10.1074/jbc.M109214200. ...
Interferon regulatory factor 6 (IRF6) is a novel and unique member of the IRF family of transcription factors, and the regulation and function of IRF6 remain unknown. Recently, IRF6 was shown to be...
Nemeckova, S.; Smahel, M.; Hainz, P.; Mackova, J.; Zurkova, K.; Gabriel, P.; Indrova, M.; Kutinova, L.. Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules. [rok vydání 2008, impact factor 1.208]. ...
DNA actively 58-49-1 biological activity down-regulates the gene expression of LL37 in monocytes and epithelial cells. Nevertheless, due to the fact
In this article explain the finer points of the delta-delta-CT method to calculate up-/down- regulations. The following text is a writeup of a course I gave at a local highschool.
TY - JOUR. T1 - Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine. AU - Mao, Li Min. AU - Wang, Wei. AU - Chu, Xiang Ping. AU - Zhang, Guo Chi. AU - Liu, Xian Yu. AU - Yang, Yuan Jian. AU - Haines, Michelle. AU - Papasian, Christopher J.. AU - Fibuch, Eugene E.. AU - Buch, Shilpa. AU - Chen, Jian Guo. AU - Wang, John Q.. PY - 2009/5/1. Y1 - 2009/5/1. N2 - Plastic changes in glutamatergic synapses that lead to endurance of drug craving and addiction are poorly understood. We examined the turnover and trafficking of NMDA receptors and found that chronic exposure to the psychostimulant amphetamine (AMPH) induced selective downregulation of NMDA receptor NR2B subunits in the confined surface membrane pool of rat striatal neurons at synaptic sites. This downregulation was a long-lived event and was a result of the destabilization of surface-expressed NR2B caused by accelerated ubiquitination and degradation of crucial NR2B-anchoring proteins by the ...
Aberrant monocyte mediator production is pivotal in the development of posttrauma immunosuppression. We have previously shown that immunodepressed trauma patients monocytes produce elevated interleukin-6, suggesting their in vivo preactivation. This study confirms that preactivated patients Mo produce greater levels of IL-6 than normals Mo to the same in the in vitro Fc gamma RI stimulation. We also demonstrate the capacity of interleukin-4 to downregulate the elevated interleukin-6 production of trauma patients in vivo preactivated monocytes. Monocyte interleukin-6 downregulation by interleukin-4 is dose dependent and occurs whether Fc gamma RI cross-linking, muramyl dipeptide, indomethacin plus muramyl dipeptide, or interferon-gamma plus muramyl dipeptide is the interleukin-6 inducing stimulus. Furthermore, interleukin-4-dependent downregulation of monocyte interleukin-6 expression is confirmed at both the supernatant and the mRNA levels. Simultaneous downregulation of posttrauma elevated
We then investigated how AIMP2 can mediate the ubiquitylation of TRAF2. AIMP2 itself did not show any of the E1, E2 or E3 enzyme activities that are the key components of ubiquitin coupling systems (data not shown). We then checked the possibility that AIMP2 facilitates the association of E3 ubiquitin ligase to its target proteins using c-IAP1, which is the known ubiquitin ligase responsible for the ubiquitylation of TRAF2 (Li et al., 2002; Wu et al., 2005). To determine the importance of c-IAP1 for AIMP2-dependent downregulation of TRAF2, we suppressed the expression of c-IAP1 and checked whether AIMP2 could still reduce the TRAF2 level. In control-siRNA-transfected cells, transfection of AIMP2 decreased TRAF2 levels (Fig. 5A, left). However, when c-IAP1 expression was suppressed with its specific siRNA, this effect of AIMP2 on TRAF2 levels was not observed (Fig. 5A, right), implying the importance of c-IAP1 for the effect of AIMP2 on TRAF2. To see whether AIMP2 would facilitate the binding of ...
Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host ...
Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host ...
Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host ...
Increased Renal Methylglyoxal Formation with Down-Regulation of PGC-1α-FBPase Pathway in Cystathionine γ-Lyase Knockout Mice. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Methods and results We confirmed that AGXT2L1 was down-regulated in liver cancer samples by immunohistochemical (IHC) staining. We also demonstrated that this down-regulation was associated with several clinicopathological features such as alpha fetoprotein (AFP) serum level and T stage. Furthermore, we showed with Kaplan-Meier analysis that expression of AGXT2L1 in tumour samples was significantly correlated with patient prognosis. The bioinformatic tool indicated that AGXT2L1 plays a role in the lipid metabolic process of HCC tissue, while siRNA silenced the expression of AGXT2L1 in HCC 97H and LM3 cells, confirming that down-regulation of AGXT2L1 promotes the lipogenesis of cancer cells. ...
miR-145 was reproducibly elevated in all the resistant sub-lines tested within one of the experimental sets; however, modulation of miR-145 levels alone in these cells did not affect their response to cisplatin. A potential target of miR-145 is cyclin dependent kinase 6 (CDK6), an important regulator of cell proliferation. Both mRNA and protein levels of CDK6 are down regulated in the resistant sub-lines. An inhibitor of CDK4/6 (PD0332991) protected cells from cisplatin cytotoxicity. ...
The present invention concerns methods and compositions for identifying genes or genetic pathways modulated by miR-15, miR-26, miR-31, miR-145, miR-147, miR-188, miR-215, miR-216, miR-331, mmu-miR-292-3p, and using nucleic acid comprising all or part of the miR-15, miR-26, miR-31, miR-145, miR-147, miR-188, miR-215, miR-216, miR-331, mmu-miR-292-3p sequences to modulate a gene or gene pathway, using this profile in assessing the condition of a patient and/or treating the patient with an appropriate miRNA.