Regarding your promoter question: yes, but its hard. if you put it there specially to have it expressed, then obviously you have an active promoter (unless youre utterly stupid). But there are plasmids that do not have promoters at all: they are only meant to make the bacteria copy the gene, not to express it. if you have the name of your plasmid, you can usually check with the manufacturer, they will have a map that will tell you what your promoter is. if its a viral promoter then youre all set. If its not, you dont really know unless you search the literature for it. Generally speaking though, a promoter WILL express your gene - thats what a promoter does. Its just that a lot of promoters arent active all the time. For example, the lac promoter is not active if the bacterium doesnt have a CAP protein ...
CIB1 is an important regulatory molecule that is expressed in different tissue types and has various binding partners.11-14 However, the role of CIB1 in ECs has never been explored. In this study, we use in vitro, ex vivo, and in vivo complementary analyses to provide the first evidence describing the critical role of CIB1 in EC function and signaling, growth factor-induced angiogenesis, and ischemia-induced pathological and adaptive angiogenesis.. Recent evidence suggests that CIB1 contributes to important intracellular signaling mechanisms. For example, we previously demonstrated that CIB1 binds to and activates PAK1 in different cell types and that CIB1 depletion results in decreased PAK1 activation on adhesion to fibronectin.14 Furthermore, we previously observed a Cdc42-dependent upregulation of PAK1 activity in CIB1-depeletd rat embryo fibroblasts with extended adhesion to fibronectin.14 In agreement with this, we also observed significantly reduced adhesion-induced PAK1 activation in ...
In this particular case, RU486 essentially prevented gene upregulation (Cd44, Stat1, Ch25h and Il1b) or downregulation (C1qa and Hexb) by LPS ...
Every single lane received equivalent quantities of protein and detection of GAPDH served as an additional loading manage. Up-regulation of hCG was observed in
actually the cause has to do with the adaptation of the eye to light. the darkness causes all the retinen in cone cells to associate with its opsin partner, leading to an increased sensitivity of the cell to intense light. When the light is turned on, it overwhelms the receptor. It takes a few minutes for the eye to adapt and to switch from rod cells to cone cells. I believe the term for this is receptor up-regulation ...
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In this study, we investigated the miRNA profile during IPC and identified the selective miRNA changes early after the IPC by comparison with normal and ISC brains. The 8 miRNAs selected in the IPC 3-hour group were categorized into 2 families of miRNAs: the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) and the miR-182 family (miR-182, miR-183, and miR-96). Among them, miR-200b, miR-200c, and miR-429 targeted PHD2 and had the best neuroprotective effect. Our data can be used for further researches into the IPC mechanism and can contribute to the development of neuroprotective miRNA therapeutics.. Several previous studies have investigated miRNAs as mediators of ischemic tissue damage. In the ischemia of cardiac myocytes, miR-199a is acutely downregulated as early as 30 minutes after ischemia, leading to rapid upregulation of its target HIF-1α,24 which suggests that the changes in miRNA in response to the ischemia seem to be very prompt. Given that the maximum ...
TF is overexpressed in many types of human cancers, and clinical studies have shown a correlation between the levels of TF expression and poor prognosis (22-25). Not only does TF expression occur in a wide spectrum of cancers, but also the level of expression in cancer cells is upregulated by 1,000-fold compared with the levels of normal cells that these cancer cells are derived from (26, 27). This drastic upregulation may, to some extent, be caused by the existence of common tumor microenvironmental stimuli, such as those responsible for TF upregulation during inflammation and hypoxia. Recently, it was shown that TF expression is under the direct control of oncogenic pathways activated by genetic mutations sustained by cancer cells (28). This is shown experimentally by the effect of several mutant oncogenes, including K-ras, EGFR, EGFRvIII, HER-2, and PML-RARa on TF transcription, translation, half-life, and encryption. The effect of these oncogenes was operative in colorectal, mammary, ...
Up-regulation of MMP-13 by IL-1Ra siRNA.(A) MMP-13 mRNA expression in IL-1Ra and control siRNA-transfected cells. The cells were cultured for 1, 3, 6, 12, and 2
EPA-induced translational up-regulation of reporter genes fused to BRCA1 mRNAb 5′UTR is dependent on the presence of tandem uORFsThe plasmid encoding for F-lu
Issues , ER whorl formation has been observed upon experimental up-regulation of a variety of membrane-anchored proteins such as cytochrome P450 , HMG-CoA
Function: Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization ...
We now know that colonic tumors increasingly express progastrins (PG) as they progress through hyperproliferative (Hp) / adenoma (Ad) / adenocarcinoma (AdCA) sequence. We and others have recently reported that autocrine PG up-regulates expression of stem-cell-markers DCLK1/CD44/LGR5 (Gastro, 2011; IJC, 2012). Two major isoforms of DCLK1 (DCLK1-S, DCLK1-L) have been reported in neuroprogenitor cells. The two isoforms were discovered to be similarly expressed in colonic epithelial cells. Regulatory effects of PG were examined on the two isoforms in normal/cancer cells. Specific primer sets were designed to amplify S and L transcripts using qRT-PCR. Colon cancer cells either expressed S (HCT-116) or both S and L forms (HT-29, DLD1). HEK293 cells were used as a model of non-transformed cells since they respond to PG, do not express autocrine PG, and are non-tumorogenic. PG significantly up-regulated both the transcripts in HEK293 cells. The L-isoform is transcribed by the 5 promoter of the gene ...
The tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. While signaling cascades downstream of HER2 and HER3 have been studied extensively at the level of post-translational modification, little is known about the effects of HER2/HER3 overexpression and activation on gene expression in breast cancer. We have now defined the genetic landscape induced by activation of the HER2/HER3 unit in mammary cells, and have identified interleukin (IL)8 and CXCR1 as potential therapeutic targets for the treatment of HER2/HER3-overexpressing breast cancers. Three-dimensional (3D) cultures, invasion and migration assays were used to determine the effects of HER2 and HER3 co-expression and activation. Gene expression analysis was performed to identify the gene network induced by HER2/HER3 in 3D cultures. Bioinformatic analysis and neutralizing antibodies were used to
05). These data obviously showed that upresgulation of miR-451 might effectively enhance the sensitivity of A549 cells to DDP. Figure 5 Effect of miR-451 upregulation on the in. vitro sensitivity of A549 cells to DDP. A. Effects of various concentrations (0, 5, 10, 15, 20 and 25 μg/ml) of DDP on cells (mock A549, A549/miR-NC or A549/miR-451) for 12 h assessed by MTT assay. B. Effects of 5 μg/ml DDP on cells (mock A549, A549/miR-NC or A549/miR-451) for varied time length (0, 12, 24, 36 and 48 h) evaluated by MTT assays. C. Effects of 5 μg/ml DDP on colony formation of cells (mock A549, A549/miR-NC or A549/miR-451). All experiments were performed in triplicate, * P < 0.05. Upregulation of miR-451 enhances DDP-induced apoptosis of A549 cells The precise underlying mechanisms by which upregulation selleck of miR-451 enhances chemosensitivity of A549 cells to DDP were further investigated. Then, the apoptosis was detected by flow cytometric assay. As shown in Figure 6A, the apoptotic rare of ...
A major challenge in the HIV field has been to understand why the strength of virus-specific CD8 T cell responses has no relationship to viral load, and yet CD8 depletion studies indicate that these cells are critical for immune control. And a major challenge in the field of immunology in general has been the rapid translation of advances in murine models to humans. In late 2005, through a telephone conversation with Rafi Ahmed, we became aware of yet unpublished data in the mouse model of chronic infection. His laboratory had shown that in mice persistently infected with LCMV, T cells up-regulate a surface molecule termed PD-1, for programmed death-1, a negative immunoregulatory molecule that turned off CD8 T cell function. The potential parallels with HIV were immediately obvious to us-perhaps persistent exposure to HIV was having a similar impact on CD8 T cell function in humans, and perhaps similar immune regulation was rendering CD4 T cells exhausted as well.. We immediately formed a ...
CONCLUSIONS: The stimulation of occlusal trauma upregulates expressions of PN(3) mRNA and NaN mRNA, which suggests the signal occurring and conduction of chronic pain by occlusal trauma have the same molecular mechanism of sodium channel as inflammatory pain. ...
PURPOSE and BACKGROUND Cancers cells grow without the vices of responses control systems, leading to increased tumor cell success. platelets, tumor cells up-regulated down-regulated and anti-apoptotic pro-apoptotic genetics, elevated the amount of cells in the activity of DNA and reduced the accurate amount in the quiescent stage, elevated phrase of cyclins, DNA fix MAPKs and …Read More. ...
In the present study we addressed the question of whether the biosynthesis of secondary carotenoids in H. pluvialisproceeds via an independent second pathway that operates outside the chloroplast, as the accumulation of the astaxanthin esters in cytosolic lipid vesicles might indicate. According to our data for PDS, we conclude that, at least for this relatively early biosynthetic step of carotenogenesis, no second cytosolic pathway exists and that higher biosynthetic activity is coupled to higher amounts of enzyme. Up-regulation on both the mRNA and protein levels was observed upon induction of SC synthesis. Because of slight variability in the extent of SC accumulation between parallels (Grünewald, 1997), we do not interpret the small difference between the maxima in PDS mRNA and protein levels as a sign for post-translational regulation events-at least the main part of up-regulation takes place at the mRNA level.. Bouvier et al. (1998) showed that pepper PDS mRNA increased under different ...
Regulation of cell migration by changes in oxygen availability is a central event during the organization of host response in inflammatory and neoplastic diseases as it may influence leukocyte recruitment and activation, angiogenesis, and metastasis formation (16). Here, we report that Hyp mediates selective up-regulation of CXCR4 in different cell types, including mononuclear phagocytes (monocytes, MDMs, and TAMs), endothelial cells, and cancer cells, and demonstrate that oxygen levels act as an important regulator of CXCR4 receptor expression. Our data also indicate that HIF-1 activation is involved in the Hyp-dependent up-regulation of CXCR4 expression and that the Hyp-HIF-1-CXCR4 circuit may participate in pathophysiological mechanisms under several conditions, ranging from inflammation to tumor angiogenesis and metastasis.. In contrast to standard cell culture conditions, characterized by 20% oxygen concentration, cells in the human body are exposed to much lower oxygen concentrations, ...
That said, we should be careful in attributing adverse pregnancy outcomes due to preeclampsia in human pregnancy to maternal stress without clear data. The association opens the door for women to blame themselves for having too much stress in their lives and therefore being responsible for their bad outcome. A number of us have tried to find cytokine markers that would serve as markers or predictors of preeclampsia - without much success. There are may be some statistical associations - but the overlap in data point is usually very large ...
Varga ZV, Kupai K, Szucs G, Gaspar R, Paloczi J, Farago N, Zvara A, Puskas LG, Razga Z, Tiszlavicz L, Bencsik P, Gorbe A, Csonka C, Ferdinandy P, Csont T: MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart., JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 62: pp. 111-121 ...
This downloadable document (GMI PUB) is filled with medically researched knowledge, relevant information and pertinent data on Superoxide Dismutase Up-regulation. The GMI PUB contains 415 abstracts which consists of a Cumulative Knowledge * of 1039. This GMI PUB document will greatly reduce your research time due to the Cumulative Knowledge feature, and contains a condensed form of the studies that we have accumulated on Superoxide Dismutase Up-regulation.. ...
This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The gene lies in a cluster of HERC family genes on chromosome 4. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments ...
An alternative essential proapoptotic protein, BAK, was not upregulated by lethal UVB doses in either early or late passage cells . BAK, in contrast to BAX, is not really acknowledged to be a transcriptional target of P. We then examined anti apoptotic proteins. BCL was downregulated by UVB in both early and late passage cells at h submit irradiation . No visible distinction was observed among passage amounts. The scenario was quite different for BCL xL. As expected , BCL xL was quickly downregulated in youthful fibroblasts starting at h publish UVB. Strikingly, the basal BCL xL degree in outdated fibroblasts was instead rapidly upregulated following UVB and reached a plateau at h . BCLxL acts by antagonistically binding to pro apoptotic partners such as BAX. We for this reason quantitated the adjust in BAX BCL xL ratio among very low and high passage ranges . In youthful cells , this ratio increased fold h right after UVB however it was unchanged during the old cells . This end result displays ...
Hi Naomi Thanks for the reply. The issue isnt necessarily low expressing genes, but perhaps high expressing genes with a small (ish) fold change. DESeq seems to only report as significant differences that are high fold changes. Contrast this to limma for microarrays, where small fold changes can be reported as significant. For whatever reason, the transcriptomic community have become fixated on two-fold as some kind of standard cut-off. Now, Im not fixated on that, but the example in DESeq reports 428 significant genes with an estimated fold change at FDR 5%, however, NONE of these are in the range -2 : 2. The minimum positive logFC is 2.18 (4.5 fold up-regulation), and the maximum negative logFC is 2.49 (5.65 fold down-regulation). So what I am concerned about is finding genes, either highly or lowly expressed, that are differing by a small fold change - say two-fold. Thanks Mick ________________________________________ From: Naomi Altman [naomi at stat.psu.edu] Sent: 14 June 2010 17:42 To: ...
Here we developed the new TS:YSOG3 reporter and used it along with TS:YSOG2 to characterize PKMζ and PKCλ turnover after cLTP induction in neurons. We found that PKMζ is upregulated following cLTP and that PKMζ copies produced after stimulation localized to synapses. We additionally demonstrated that the turnover of PKMζ copies synthesized after cLTP is more rapid than the turnover of basal PKMζ, both in the neuron cell body and in dendritic spines. These results held for PKMζ fused via its C terminus to TS:YSOG2. Furthermore, we demonstrated that PKCλ remains more stable at synapses than PKMζ and that its turnover is not altered after cLTP. We showed that our TS reporters not only allow identification of new copies of a given protein but also old copies as they degrade over time; this is possible because TS-tagged proteins synthesized during BILN application remain fused to irreversibly complemented YFP that stays stable after BILN washout. Moreover, fusion to TS did not affect PKMζ ...
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strong evidence that transcriptional repression plays a major role in regulating GARAPL1/MAP1LC3A levels, and this up-regulation results in an increase in the size of the autophagosome ...
This unexpected set of observations led the investigators to explore a role for APE1 in regulation of nitric oxide synthase activity. Within the vascular endothelium, endothelial nitric oxide synthase (eNOS) activity is affected by levels of expression and also by well-characterized signaling pathways that activate eNOS. Expression of eNOS cannot be the major determinant of the hypertensive phenotype of APE1+/− mice, because eNOS levels are actually increased in the vessels of these mice in spite of their impaired ability to generate nitric oxide. The effect seems to be at the level of eNOS activation. Based on the data presented in this report it is reasonable to conclude that this is due in part to upregulation of H-Ras, which lies upstream of the phosphoinositide-3 kinase/Akt kinase pathway that potently activates eNOS.. The investigators conclude that increased Akt activation occurs via APE1-dependent upregulation of H-Ras expression, although the effect on H-Ras is modest and other ...
A MADS-box gene, designated PtAP3, was isolated from a floral bud cDNA library derived from Populus tomentosa. Analysis by multiple alignments of both nucleotide and amino acid sequences, together with phylogenetic analysis, revealed that PtAP3 is an ortholog of Arabidopsis AP3. Analysis of RNA extracts from vegetative and reproductive tissues of P. tomentosa by RT-PCR indicated that PtAP3 is expressed in roots, stems, leaves and vegetative and floral buds. Notably, the expression of PtAP3 fluctuated during floral bud development between September and February with differences between male and female buds. In the former, a gradual down-regulation during this period, interrupted by a slight up-regulation in December, was followed by a sharper up-regulation on February. In developing female floral buds, expression was stable from September to November, sharply up-regulated in December, and then gradually down-regulated until February. The functional role of PtAP3 was investigated in transgenic ...
CS1 (CD319) is a member of the SLAM family of receptors, expressed on NK cells, T cells, B cells, DCs, etc. It induces NK cell cytotoxicity and is up regulated on B cell activation. CS1 is aberrantly up regulated on B cells in multiple myeloma and a therapeutic humanized anti-CS1 mAb HuLuc63 (Elotuzumab) is in Phase III of clinical trials. Recently, a unique population of CS1high B cells, implicated as major producers of pathogenic auto antibodies was detected in high SLE disease activity index (SLEDAI) patients. Regression analysis indicated direct correlation between the percentage of CS1high B cells and SLEDAI. With the available information on the pathogenic outcome of CS1 up-regulation on B cells, it is vital to study the molecular basis of CS1 expression. Here, we discuss the transcriptional regulation of mouse CS1 gene. According to our data, mouse CS1 promoter binds to Blimp1, mainly a trans-repressor and the master regulator of B cell maturation. Interestingly, mCS1 promoter also bears ...
FMRP has emerged as a central player in the regulation of protein synthesis-dependent synaptic plasticity. However, we know very little about how FMRP expression itself may be regulated as a function of neural activity in vivo, particularly during the time course over which major changes in synaptic reorganization occur. To address this question, we have determined the role of visual experience in regulating FMRP expression in the visual cortex of DR/LE rats. The most striking finding is that experience induces a rapid but transient expression of FMRP in this system. Furthermore, this transient upregulation of FMRP is observed in both dendrites and cell bodies and requires NMDA receptor activation. Our findings suggest that FMRP plays a dynamic role in experience-induced plasticity, especially during the first 15 min of synaptic reorganization.. We used both biochemical and immunohistochemical methods to study experience-dependent FMRP regulation. Immunolocalization revealed that, 15 min after ...
Ishikawa, K., Miyamoto, M., Yoshioka, T., Kato, T., Kaji, M., Ohbuchi, T., Hirano, S., Itoh, T., Dosaka-Akita, H. and Kondo, S. (2008), Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis. Cancer, 113: 530-541. doi: 10.1002/cncr.23618 ...
Thus we questioned whether IL-4-producing CD8 T cells would be induced in vivo in response to primary immunization with alum-precipitated protein. The approach has been to compare the polarization of transgenic naïve ovalbumin-specific CD4 (OTII) and CD8 (OTI) T cells during their response to alum-precipitated ovalbumin (alumOVA). By addressing this question we have obtained further insight into the way early Th2-features are acquired by CD4 T cells in vivo in response to alum-precipitated protein.. Although both CD4 and CD8 OVA-specific T cells proliferate (30) in response to alumOVA, the acquisition of Th2-features, such as IL-4 and IL-13 mRNA up-regulation, is exclusively confined to CD4 T cells (Fig. 2). In addition, we confirm that mRNA specific for IL-17RB is strongly induced in vivo in alumOVA-responding OTII cells, but not in OTI cells responding to the same antigen (Fig. 2).. Conclusions. These findings indicate that the induction of IL-17RB expression is a selective feature of CD4 T ...
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Propranolol order uk. This of course raises the question of what is repressed, and how this prлpranolol turn leads to the up-regulation of Snail and slug, which are also repressors.
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Pharmacological interference with vacuolar-type H(+)-ATPase (V-ATPase), a proton-translocating enzyme involved in protein transport and pH regulation of cell organelles, is considered a potential strategy for cancer therapy. Macrophages are critically involved in tumor progression and may occur as pro-tumoral M2 phenotype, whereas classically-activated M1 can inhibit tumor development for example by releasing tumor-suppressing molecules, including tumor necrosis factor (TNF)alpha. Here, we show that targeting V-ATPase by selective inhibitors such as archazolid upregulates the expression and secretion of TNFalpha in lipopolysaccharide (LPS)- or LPS/interferon (INF)gamma-activated M1-like macrophages derived from human blood monocytes. In contrast, archazolid failed to elevate TNFalpha production from uncommitted (M0) or interleukin (IL)-4-treated M2-like macrophages. Secretion of other relevant cytokines (i.e., IL-1beta, IL-6, IL-10) or chemokines (i.e. IL-8 and monocyte chemotactic protein-1) ...
TY - JOUR. T1 - PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer. AU - Juang, Yu Lin. AU - Jeng, Yung Ming. AU - Chen, Chi Long. AU - Lien, Huang Chun. PY - 2016. Y1 - 2016. N2 - TGF-β and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-β biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-β continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-β and identified TGF-β-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by ...
Participants who passed the oral meals challenge at 24 months and consumed the complete cooked egg were instructed to add egg with their diet advertisement libitum and to report any adverse occasions. Egg consumption and adverse events were ascertained by telephone or at clinic visits at 30 months and 36 months. Immune Markers Skin-prick testing with egg extract and saline and histamine controls was performed at enrollment and at 10 months and 22 months. Basophil activation was measured relating to CD63 up-regulation on flow cytometry.24 Serum egg-particular IgE and IgG4 antibody amounts were measured with the use of the ImmunoCAP 100 . Statistical Analysis We calculated a sample of 55 participants would provide 84 percent power, at a two-sided alpha level of 0.05, to detect a substantial between-group difference in the rate of sustained unresponsiveness, assuming around 10 percent rate in the placebo group and around 50 percent rate in the oral-immunotherapy group.$750 million needed to deal ...
The lower risk of coronary artery disease in premenopausal women than in men and postmenopausal women implicates sex steroids in cardioprotective processes. in the presence of \estradiol. Our results indicate that the protein upregulation of LDLR at subtranscriptionally 528-48-3 supplier effective doses of \estradiol, and its supratranscriptional upregulation at 10?m \estradiol, occur through an extracellular PCSK9\dependent mechanism. can be induced by estrogen through the estrogen receptor (ER) but not through the classic estrogen\responsive element site, which is absent in the promoter region 7. Instead, ER induces transcription by its interaction with specific factor\1 sites 8. Androgen does not increase the transcription of transcription contributed to the downstream effect of elevated LDLR expression levels observed in rats in response to estradiol 23. In humans, plasma PCSK9 levels are significantly higher in premenopausal, age\matched women than in men, despite significantly lower LDLC ...
INTRODUCTION: Preservation of structure and function of the myocardium is critically dependent upon improving the survival of existing cardiomyocytes (CM), through strategies that limit CM apoptosis and DNA damage. BRCA1 is a tumor suppressor gene which functions to promote DNA repair, and protect cells against oxidative and genotoxic stress. We hypothesized that BRCA1 is a novel cellular target to limit CM apoptosis, and prevent aberrant cardiac remodeling.. METHODS AND RESULTS: Experimental MI in mice caused a profound 16-fold upregulation in BRCA1 expression, which peaked at 72 hours (p,0.01). In vitro gain-of-function experiments demonstrated that Ad-BRCA1 overexpression protected neonatal rat CM against doxorubicin- and H2O2-induced apoptosis, as assessed by FACS (p,0.01) and activated caspase-3. Ad-BRCA1-expressing CM exhibited a profound reduction in p53 expression in response to doxorubicin and H2O2. Co-immunoprecipitation studies demonstrated a distinct physical interaction of BRCA1 ...
Although the theory once met with skepticism, it has become clear that use of β-blockade in congestive heart failure due to systolic dysfunction can improve symptoms, increase EF, and probably improve longevity.1 2 3 4 12 24 25 26 Mechanisms proposed for the effectiveness of β-blockade in heart failure have included (1) improved β-receptor function,6 (2) protection of the myocardium from the effects of prolonged exposure to high levels of circulating catecholamines,9 and (3) that bradycardia that usually accompanies β-blockade might be beneficial for improvement of myocardial energetics.27 Clearly, some β-blockers in heart failure cause β-receptor upregulation and improve β-receptor function.6 However, because the β-receptors are chronically blocked by the therapy itself, β-receptor upregulation is probably most important in response to acute increases in catecholamines, such as might occur during exercise. On the other hand, recent studies in our laboratory demonstrated that ...
Tobacco addiction remains a leading preventable cause of premature deaths worldwide, and the long- term efficacy of current smoking cessation treatments is mode...
Our results showed both similarities and differences between the source paper data. The source paper indicated that in conditions of oxygen limitation the cell would up-regulate the use of cytochromes, up-regulate the use of NAD+/NADH independent enzymes such as ferredoxin enzymes, and up-regulate the use of hydrogenases. All of these changes were a means of conserving energy and oxygen in the cell and more efficiently using the resources available to the cell. Out decreased expression ontologies are almost all related to pathways that involve the utilization of NAD+/NADH for cellular energy. This is consistent with the sources papers conclusion of the up-regulation of NAD+/NADH independent enzymes. If NAD+/NADH independent enzymes are being up-regulated then it stands to reason that NAD+/NADH dependent enzymes would be down-regulated to avoid excessive interference with the independent enzymes. Our increased ontologies show the up regulation of numerous regulatory pathways. This is consistent ...
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Ive run across this on Heartfixer and several forums: Sulfite is neurotoxic. Sulfite will be over produced by the CBS up regulation, and then...
article{b05afb58-252f-4a27-a2c1-eeed80e365a7, author = {Möller, Sebastian and Uddman, Erik and Welsh, Nicola and Edvinsson, Lars and Adner, Mikael}, issn = {1879-0712}, language = {eng}, number = {2-3}, pages = {209--215}, publisher = {Elsevier}, series = {European Journal of Pharmacology}, title = {Analysis of the time course for organ culture-induced endothelin ET(B) receptor upregulation in rat mesenteric arteries.}, url = {http://dx.doi.org/10.1016/S0014-2999(02)02499-8}, volume = {454}, year = {2002 ...
The pharmacological modulation of putative renoprotective factors hypoxia-inducible factor-1α (HIF-1α) and HIF-1α-regulated vascular endothelial growth factor-A (VEGF-A) in the kidney has therapeutic interest. In human renal proximal tubular HK2 cells, prostaglandin E2 (PGE2) up-regulates HIF-1α and VEGF-A through epidermal growth factor receptor (EGFR)-dependent up-regulation of retinoic acid receptor-β (RARβ). Here we studied the role of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 and their target kinase, mitogen- and stress activated kinase-1 (MSK1), in the signaling cascade. Treatment of HK2 cells with PGE2 resulted in increased phosphorylation of EGFR, the three studied kinases and the histone H3 (Ser10) at the RARβ gene promoter (the latter has been proposed as a molecular signature of the activated RARβ gene promoter). Prevention of the phosphorylation of EGFR, ERK1/2, p38 MAPK or MSK1 is by incubating, respectively, with AG1478, PD98059, SB203580 or H89 allowed to ...
The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO ...
The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO ...
Background Myocyte stress 1 (MS1) is a striated muscle actin binding protein required for the muscle specific activity of the evolutionary ancient myocardin related transcription factor (MRTF)/serum response factor (SRF) transcriptional pathway. To date, little is known about the molecular mechanisms that govern skeletal muscle specific expression of MS1. Such mechanisms are likely to play a major role in modulating SRF activity and therefore muscle determination, differentiation and regeneration. In this study we employed a comparative in silico analysis coupled with an experimental promoter characterisation to delineate these mechanisms. Results Analysis of MS1 expression in differentiating C2C12 muscle cells demonstrated a temporal differentiation dependent up-regulation in ms1 mRNA. An in silico comparative sequence analysis identified two conserved putative myogenic regulatory domains within the proximal 1.5 kbp of 5 upstream sequence. Co-transfecting C2C12 myoblasts with ms1 ...
... in the field of allergy. even when they are not given until after starting HgCl2 administration. IFN- is definitely a pivotal cytokine in ameliorating the Th2 response and actions aimed at selective up-regulation of this cytokine may be of restorative value in suppression of undesirable IgE reactions. < 005 was taken to indicate statistical significance. RESULTS Exogenous type-1 cytokines suppress IgE production in HgCl2-treated BN rats HgCl2 treatment of BN rats resulted in designated elevation of serum IgE concentrations, as previously reported [7]. IgE levels were barely above normal at day time 7, then rose rapidly to maximum levels by day time 14. Administration of exogenous recombinant rat IFN- at a dose of 6 104 U/day time Motesanib had little effect (= 069, two-tailed MannCWhitney = 0009 HgCl2 only, = 001 group treated with 6 104 U/day time; two-tailed MannCWhitney = 0026). IgE levels at day time 14 were ...
Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.
The modern diet is greatly different from that of our paleolithic forebears in a number of respects. There is reason to believe that many of these dietary shifts can up-regulate intracellular signalling pathways mediated by free intracellular calcium and protein kinase C, particularly in vascular smooth muscle cells; this disorder of intracellular regulation is given the name PKC syndrome. PKC syndrome may entail either a constitutive activation of these pathways, or a sensitization to activation by various agonists. The modern dietary perturbations which tend to induce PKC syndrome may include increased dietary fat and sodium, and decreased intakes of omega-3 fats, potassium, calcium, magnesium and chromium. Insulin resistancemay be both a cause and effect of PKC syndrome, and weight reduction and aerobic training should act to combat this disorder. PKC syndrome sensitizes vascular smooth muscle cells to both vasoconstrictors and growth factors, and thus promotes both hypertension and ...
It has been reported that median survival duration of Indian ALS patients is ~9 years after disease onset which is significantly higher as compared to their Western counterparts who survive for 3-6 years after disease onset [6-8]. Because of this contradicting presentation, we investigated the levels of VEGF-A and CCL2 among the Indian ALS patients.. The increased PBMCs VEGF-A and CCL2 expression in our patients may suggest the pathophysiological involvement of circulating monocytes and lymphocytes in ALS. The elevated PBMCs VEGF-A is in contrast to previous reports where a profound downregulation of VEGF-A mRNA in SOD1G93A ALS mouse and significantly reduced serum and cerebrospinal fluid (CSF) VEGF-A in ALS patients was observed possibly because of genetic changes in promoter regions [15-17]. Increased serum and CSF VEGF-A reported earlier in ALS and in its different clinical subtype with limb onset and extended disease duration are in agreement with current results [18, 19]. However, some ...
Results Under basal conditions, freshly isolated T cells from active lupus patients had 2.3-fold higher miR-21 levels compared to healthy T cells. Combined anti-CD3/anti-CD28-stimulation induced higher miR-21 levels in SLE T cells than in controls (mean 4.0-fold vs 1.6-fold, respectively), suggesting aberrant regulation of miR-21 expression in SLE. PD-1 mRNA and miR21 levels correlated with disease activity. There was an inverse correlation between PD-1 mRNA and miR-21 levels in SLE patients (r2=−0.93) suggesting a co-regulation. This was documented by stimulating SLE T cells with anti-CD3/anti-CD28 in the presence or not of PDL1.Ig. PD-1 cross-linking reduced miR-21 levels by 45%. Moreover, silencing of PD-1, using a specific siRNA, was associated with 4.5-fold up-regulation of miR-21. Experiments are underway to elucidate the mechanisms of transcriptional regulation of miR-21 by mediators downstream to PD-1 and to correlate PD-1 genotypes with mir-21 expression.. ...
Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumors upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether a bulky glycocalyx promotes a tumor phenotype by increasing integrin adhesion and signaling. Data revealed that a bulky glycocalyx facilitates integrin clustering by funneling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumor-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signaling to support cell growth and survival. Clinical studies revealed that ...
Dr. Walkers lab will use in vitro experiments to determine the functional consequences of upregulating a dominant negative version of the prolactin receptor. She will use both human and mouse breast cancer cells and analyze the effects of this upregulation on cell survival, proliferation, differentiation, migration, invasion, cell markers of stemness, and the ability of cells in the culture to form mammospheres. The results of her study will help to clarify the potential ability of her therapeutic strategy to slow or halt the growth and spread of tumors, and to eradicate tumor stem cells. ...
Genetic studies implicate Fgf10-Fgfr2 signaling as a critical regulator of bud morphogenesis in the embryo. However, little is known about the transcriptional targets of Fgf10 during this process. Here we identified global changes in gene expression in lung epithelial explants undergoing FGF10-mediated budding in the absence of other growth factors and mesenchyme. Targets were confirmed by their localization at sites where endogenous Fgf10 signaling is active in embryonic lungs and by demonstrating their induction in intact lungs in response to local application of FGF10 protein. We show that the initial stages of budding are characterized by marked up-regulation of genes associated with cell rearrangement and cell migration, inflammatory process, and lipid metabolism but not cell proliferation. We also found that some genes implicated in tumor invasion and metastatic behavior are epithelial targets of Fgf10 in the lung and other developing organs that depend on Fgf10-Fgfr2 signaling to properly ...
Sigma-Aldrich offers abstracts and full-text articles by [Hai Zhang, Shanyu Cheng, Min Zhang, Xiuping Ma, Li Zhang, Yipin Wang, Rong Rong, Juan Ma, Shukai Xia, Mingzhan Du, Feng Shi, Jie Wang, Qinyi Yang, Xiaoming Bai, Jing Leng].
Deals, coupons, events, images, phone number, directions, and whats nearby Therapeutic Solutions PC, a doctor business at 3247 Esplanade, Chico, CA 95973 on Fave.
misc{9ad9b9f4-306e-41a1-8e16-4835068ccfb9, author = {Zheng, J and Zhang, Y and Edvinsson, Lars and Xu, C. -B}, issn = {1473-5598}, language = {eng}, note = {Conference Abstract}, number = {Suppl. 1}, pages = {24--24}, publisher = {Lippincott Williams & Wilkins}, series = {Journal of Hypertension}, title = {Vascular endothelin type B receptor upregulation correlates with activation of inflammatory transcriptional factor NF-kappaB}, volume = {26}, year = {2008 ...
We have found that serotonin (5-HT), the endogenous monoamine that mediates dishabituation and sensitization, causes upregulation of AMPA receptor function in Aplysia motor neurons. This functional upregulation of AMPA receptors depends upon release of calcium from postsynaptic intracellular stores and postsynaptic exocytosis. We hypothesize that stimuli that induce dishabituation and sensitization in Aplysia modulate AMPA receptor trafficking in motor neurons that mediate that withdrawal reflex. Support for this hypothesis comes from experiments in which prior injection of botulinum toxin, an inhibitor of exocytosis, into identified siphon motor neurons blocks behavioral dishabituation of the siphon withdrawal reflex ...
Acute kidney injury (AKI) is defined by the rapid loss of kidney function due to tissue damage. It affects 10-30 % of hospitalized patients and is independently associated with increased morbidity and mortality. Ischemia-reperfusion injury (IRI) is the most common pathoetiological mechanism of AKI, whereby tissue injury is mediated by reactive oxygen species. Ischemic AKI leads to the rapid upregulation of a transmembrane protein, kidney injury molecule-1 (KIM-1) on the apical membrane of proximal tubular epithelial cells (TECs). Previous work from our group and others demonstrated that the extracellular domain of KIM-1 specifically binds to phosphatidylserine on apoptotic cells, thereby transforming KIM-1-expressing TECs into semi-professional phagocytes for apoptotic corpses. The pathophysiological role of KIM-1 in AKI and relevant signalling mechanisms have not yet been elucidated. Using an in vivo model of AKI in mice genetically deficient in Kim-1, we reveal that Kim-1 expression protects mice from
Long-term objectives and specific aims: The overall objective of this proposal is to understand the cellular mechanisms by which free fatty acids modulate hepatocyte lipoapoptosis. The specific aims are to test these hypotheses: 1. Free fatty acids upregulate expression of p53 upregulated modulator of apoptosis (PUMA). 2. Free fatty acids mediate dysregulation of Mcl-1. 3. In animal models of nonalcoholic fatty liver disease, genetic deletion of apoptosis effectors modulates liver injury ...
The CD23 antigen (also called B6) is a 45 kDa transmembrane glycoprotein associated with MHC Class II antigen, which belongs to the C-type lectin family. CD23 is the low affinity receptor for IgE (FcεRII). CD23 antigen is expressed on B lymphocytes, monocytes and follicular dendritic cells (FDC). Expression of CD23 by B lymphocytes is up-regulated following mitogen or antigen activation. Soluble forms of CD23 are generated by proteolytic cleavage of the membrane molecule ...
PHILADELPHIA - Drugs that inhibit the activity of enzymes called histone deacetylases (HDACs) are being widely developed for treating cancer and other diseases, with two already on the market. Researchers at the Perelman School of Medicine, University of Pennsylvania, show that a major HDAC still functions in mice even when its enzyme activity is abolished, suggesting that the beneficial effects of HDAC inhibitors may not actually be through inhibiting HDAC activity, and thus warranting the reassessment of the molecular targets of this class of drugs.. The study, appearing online in Molecular Cell this week, was conducted in the laboratory of Mitchell A. Lazar, M.D., Ph.D., director of the Institute for Diabetes, Obesity, and Metabolism. The Lazar lab has been working on HDAC3 for over a decade, focusing on the pivotal role of this enzyme in hormone-mediated regulation of gene expression and metabolism. They previously showed that depletion of HDAC3 in mouse liver upregulates expression of many ...
results in up-regulation of KDR receptor gene transcription and protein expression and that KDR/Flk-1 up-regulation induced by CCL23 may contribute to potentiation of VEGF action in angiogenesis (Han 2009 ...
TY - JOUR. T1 - MUC8 mucin gene up-regulation in chronic rhinosinusitis. AU - Lee, Heung Man. AU - Kim, Dae Hoon. AU - Lee, Sang Hag. AU - Kim, Jung Min. AU - Hwang, Soon Jae. PY - 2004/8/1. Y1 - 2004/8/1. N2 - The primary mechanisms leading to mucus hypersecretion in chronic sinus inflammation are not well understood. This study aims to investigate the expression of MUC8 messenger RNA (mRNA) and protein and to compare between normal and chronically inflamed sinus mucosae in terms of the expression of MUC8 mRNA. Ten patients with chronic rhinosinusitis who were undergoing functional endoscopic sinus surgery were recruited for the study. Ten patients with no evidence of sinus disease were used as control subjects. RNAs were extracted from sinus mucosa, and semiquantitative reverse transcription-polymerase chain reaction was performed for MUC8. Localization of MUC8 protein was sought by immunohistochemical analysis. Messenger RNA encoding MUC8 was detected in human sinus mucosa. The level of MUC8 ...
In this study, we evaluate the effect of HO-1 upregulation on blood pressure and cardiac function in the new model of infarct spontaneous hypertensive rats (ISHR). Male spontaneous hypertensive rats (SHR) at 13 weeks (n = 40) and age-matched male Wistar (WT) rats (n = 20) were divided into six groups: WT (sham + normal saline (NS)), WT (sham + Co(III) Protoporphyrin IX Chloride (CoPP)), SHR (myocardial infarction (MI) + NS), SHR (MI + CoPP), SHR (MI + CoPP + Tin Mesoporphyrin IX Dichloride (SnMP)), SHR (sham + NS); CoPP 4.5 mg/kg, SnMP 15 mg/kg, for six weeks, one/week, i.p., n = 10/group. At the sixth week, echocardiography (UCG) and hemodynamics were performed. Then, blood samples and heart tissue were collected. Copp treatment in the SHR (MI + CoPP) group lowered blood pressure, decreased infarcted area, restored cardiac function (left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), +dp/dtmax, (−dp/dtmax)/left ventricular systolic pressure (LVSP)), inhibited
Colon cancer cells show increased resistance to chemotherapeutic agents compared to breast cancer cells (28, 29), and the molecular mechanisms of this resistance are not fully known. While colon cancer cells express high levels of Src family kinases (30), the survival signal pathways associated with its expression are not known (31). In the present study, we have demonstrated that colon cancer cell lines have survival signals operative through both FAK and Src activities, suggesting that the combination of these signals may contribute to their resistance to apoptosis. Furthermore, these results have shown for the first time that combined dual Src and FAK inhibition is effective for inducing apoptosis in colon cancer cell lines.. Several studies have demonstrated up-regulation of FAK expression in colorectal cancer (11, 13, 14, 24, 25, 32), and it appears that colon cells up-regulate expression of FAK at early stages of tumorigenesis, even before carcinoma has been detected (11). Our previous ...
Previously we reported that the P2Y2 receptor (P2Y2R) is one of the predominant purinergic receptors expressed in human coronary artery endothelial cells (HCAEC), and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here we report a role of a newly identified AP-1 consensus sequence along with its new binding components in P2Y2R regulation of TF transcription. We identified with bioinformatics tools that a novel AP-1 site at -1363 bp of human TF promoter region is highly conserved across multiple species. P2Y2R activation increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this new distal AP-1 site all significantly supressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2 and Fra-1, but not the typical c-Fos, ...
Embryonic muscle growth requires a fine balance between proliferation and differentiation. In this study we have investigated how this balance is achieved during chick development. Removal of ectoderm from trunk somites results in the down-regulation of Pax-3 expression and cell division of myogenic precursors is halted. This initially leads to an up-regulation of MyoD expression and to a burst in terminal differentiation but further muscle growth is arrested. Locally applied bone morphogenetic protein-4 (BMP-4) to somites mimics the effect of the ectoderm and stimulates Pax-3 expression which eventually results in excessive muscle growth in somites. Surprisingly, BMP-4 up-regulates expression of noggin which encodes a BMP-4 antagonist. This suggests that the proliferation enhancing activity of BMP-4 can be limited via up-regulation of noggin and that myogenic cells differentiate, as an intrinsic property, when deprived of BMP-4 influence. In contrast to BMP-4, Sonic hedgehog (Shh) locally ...
Purpose: : To compare the mRNA expression of IL-1α, IL-8, MCP-1, and TGF-ß1 following topical ethanol treatment and mechanical debridement. Methods: : Fifty-eight pigmented rabbit corneas were divided into four groups. Group I (n=18) received mechanical epithelial debridement, group II (n=18) underwent 20% ethanol application for 30 seconds, and group III corneas underwent 20% ethanol application for 60 seconds. Group IV (n=4) did not undergo any procedure. Corneal epithelial and stromal keratocyte change was examined with H&E and TUNEL stains, while the mRNA expression of IL-1α, IL-8, MCP-1, and TGF-ß1 were examined with real-time polymerase chain reaction (PCR). Results: : Stromal keratocyte apoptosis was noticed for three days in group I and up to seven days in group III. Topical ethanol induced significant TUNEL staining of corneal epithelium and stromal keratocyte in an application time dependent manner. In group I, the expression of IL-8 mRNA showed two spikes of up-regulation on day 0 ...
Human plasmacytoid dendritic cells secrete high levels of IFNa and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN g and enhanced cytotoxicity. We show that pDC mediate these processes by different mechanisms, some of which overlap. Human NK cells were analysed after co-culture with immature or CpG-matured blood pDC or with supernatant from these cells. Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC and did not require pDC contact. Up-regulation was due in part to IFNa but also to factors in IFNa negative supernatant from immature DC. HLA-DR expression was independent of secreted molecules but required contact with immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562 targets and expression of CD107a, was mediated by multiple factors including type I IFN, supernatant from immature pDC cultures and contact with immature or mature pDC
Lipotoxicity caused by excessive fat deposition in skeletal muscle cells is a characteristic of type II diabetes, heart disease and obesity. Defining how glucose stimulates this is therefore an important goal. Isabelle Guillet-Deniau and co-workers have now dissected the signalling mechanisms involved, using contracting myotubes derived from cultured muscle satellite cells (see p. 1937). They show that glucose treatment stimulates cells to take up glucose and upregulate expression of lipogenic enzymes. The authors then demonstrate that prior to this the cells synthesize and activate sterol-regulatory-element-binding protein 1c (SREBP-1c), a transcription factor that regulates cholesterol and fatty acid metabolism. Moreover, they show that knocking down SREBP-1c by RNAi blocks glucose-induced upregulation of lipogenic enzymes. Guillet-Deniau and co-workers go on to demonstrate that stimulation of SREBP-1c requires the JAK2/STAT3 signalling pathway but is independent of insulin, which is ...
TY - JOUR. T1 - CLIC1 null mice demonstrate a role for CLIC1 in macrophage superoxide production and tissue injury. AU - Ulmasov,Barbara. AU - Bruno,Jonathan. AU - Oshima,Kiyoko. AU - Cheng,Yao Wen. AU - Holly,Stephen P.. AU - Parise,Leslie V.. AU - Egan,Terrance M.. AU - Edwards,John C.. PY - 2017/3/1. Y1 - 2017/3/1. N2 - We generated and studied CLIC1 null (C1KO) mice to investigate the physiological role of this protein. C1KO and matched wild-type (WT) mice were studied in two models of acute toxic tissue injury. CLIC1 expression is upregulated following acute injury of WT kidney and pancreas and is absent in C1KOs. Acute tissue injury is attenuated in the C1KOs and this correlates with an absence of the rise in tissue reactive oxygen species (ROS) that is seen in WT mice. Infiltration of injured tissue by inflammatory cells was comparable between WT and C1KOs. Absence of CLIC1 increased PMA-induced superoxide production by isolated peritoneal neutrophils but dramatically decreased ...
Depending on the cellular context, transforming growth factor β (TGFβ) has been observed to exert protumorigenic functions, such as inducing an epithelial-mesenchymal transition (EMT), or inhibit tumorigenesis by activating apoptosis. The proapoptotic functions of TGFβ have been linked with the transcription factor SMAD4, which acts downstream of TGFβ and is frequently deleted in pancreatic ductal carcinoma (PDAC). To elucidate the mechanism by which TGFβ promotes apoptosis, David and colleagues used a Kras-mutant/Smad4-deleted PDAC murine model and found that reintroduction of SMAD4 sensitized cells to TGFβ treatment and promoted changes in cell morphology and loss of E-cadherin consistent with EMT. Moreover, SNAIL was shown to be upregulated following TGFβ treatment, and genetic depletion of SNAIL inhibited TGFβ-induced EMT, apoptosis, and accelerated pancreatic carcinogenesis in SMAD4-wild-type cells, raising the unexpected possibility that EMT precedes apoptosis and is required for ...
The present study investigated the suitability of a sediment contact assay using zebrafish (Danio rerio) embryos to evaluate the degree of lake sediment contamination. As endpoints, developmental parameters (mortality, abnormality, heart rate, and hatching rate) as well as stress protein responses (hsp 70 levels) in the developing embryos were recorded during a 96-h exposure. Fertilized zebrafish eggs were exposed to both the whole as well as organic extract concentrations prepared from collected sediments from 5 sites along Laguna Lake, Philippines. Compared to whole sediment exposure, more severe embryotoxic and teratogenic responses were elicited in embryos exposed to organic extracts. However, since whole sediment-exposed embryos also revealed significant developmental defects, this exposure phase served as the more realistic exposure scenario in our study. Weak to strong upregulation of hsp 70 levels was also registered among embryos exposed to both whole sediments and organic extracts. The ...
Enteral feeding induced a significant up-regulation of pro inflammatory genes such as IL8 and TLR 4 in the absence of any clinical symptoms of NEC. Those effects were more distinct in the formula fed subgroup compared to piglets who received colostrum. Most up-regulated genes, particularly IL8 and TLR4, were associated with endonuclease hypersensitive regions and were thus located in de-condensed, active chromatin. In consistence with this finding, TSA pretreated Caco-2 cells exhibit a significant higher IL 8 up-regulation after LPS exposure compared to controls. ...
The purpose of this double-blind, placebo-controlled, dose-escalation study is to evaluate the safety, tolerability and effectiveness of Thymosin Beta 4 (Tβ4), administered topically, in patients with Pressure Ulcers (PU). PU is caused by prolonged pressure or rubbing of the body in areas prone to moisture and friction. PU affects primarily elderly, bedridden patients. Tβ4 is a synthetically-produced copy of a naturally-occurring 43 amino acid peptide that has wound healing and anti-inflammatory properties and can up-regulate the expression of laminin-5 ...
The purpose of this double-blind, placebo-controlled, dose-escalation study is to evaluate the safety, tolerability and effectiveness of Thymosin Beta 4 (Tβ4), administered topically, in patients with Pressure Ulcers (PU). PU is caused by prolonged pressure or rubbing of the body in areas prone to moisture and friction. PU affects primarily elderly, bedridden patients. Tβ4 is a synthetically-produced copy of a naturally-occurring 43 amino acid peptide that has wound healing and anti-inflammatory properties and can up-regulate the expression of laminin-5 ...
Astrocytes derived from Y757F mutant mice defective in gp130-SHP2/SOCS3 signaling were investigated into their ability to respond to IL-6. Compared with WT astrocytes, Y757F astrocytes treated with hyper-IL6, had higher and more sustained activation of STAT3, while the levels of pY-SHP2 and pERK remained unchanged. Gene expression was investigated by Affymetrix gene chip analysis. At 2 hr, 306 genes were upregulated in WT astrocytes and of these, 28 did not increase in Y757F astrocytes. Of 238 genes upregulated in Y757F astrocytes, 9 were not upregulated in WT astrocytes. Some 99 genes were downregulated in WT astrocytes and of those 55 were not decreased in Y757F astrocytes. In WT astrocytes after 12 hrs the level of expression of many genes was reduced back to or near levels seen in the untreated cells, however, in Y757F astrocytes 109 genes either maintained their 2hr upregulated levels or were further increased. A number of candidate genes upregulated by hyper-IL6 in WT and Y757F astrocytes ...
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.
0 0 = 0 = = 1 1 0 0 = = 0 0 0 1 = = = 1 0 = = = 1 1 = 0 0 = = = 1 = = = 1 1 = 0 0 = = 0 1 = 0 1 0 0 = = 0 = 1 1 = 1 0 = 1 = = 0 = 0 1 = 1 1 = = = = 0 = ...
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Over-expression of IL-8 has been detected in many human tumors. However, the effects of IL-8 in migration and integrin expression in chondrosarcoma cells are largely unknown. In this study, we found that IL-8 increased the migration and the expression of αvβ3 integrin in human chondrosarcoma cells. Activations of phosphatidylinositol 3-kinase (PI3K), Akt, and AP-1 pathways after IL-8 treatment were demonstrated, and IL-8-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and AP-1 cascades. Taken together, our results indicated that IL-8 enhances the migration of chondrosarcoma cells by increasing αvβ3 integrin ...
Results 202 proteins showed significant differential expression between the CAD patients and the control subjects (P , 0.05). CAD patients had selective depletion of antioxidants; glutathione peroxidase 3 (GPX3) (p , 1e-28), clusterin (p , 1e-12) and serum paroxonase-1 (PON1) (p , 1e-7) compared with controls. Furthermore, there was selective up-regulation of proteins concerned with inflammation; serum amyloid A-1 (p , 1e-12), mannan binding lectin serine protease 1 (MASP1) (p , 1e-8) and galectin-3-binding protein (p = 0.001) in the CAD patients compared with the control subjects. Phospholipid transfer protein (PLTP) (p , 0.001) and apolipoprotein (a) (p = 0.002) were over expressed in the CAD patients. ...
Clone FR3-16A11 recognizes CD203c, a glycosylated type II transmembrane molecule that belongs to the family of ecto-nucleotide pyrophosphatase/ phosphodiesterase (E-NPP3) enzymes. Among hematopoietic cells, expression of CD203c is restricted to basophils as well as to mast cells and their precursors, and has been described as specific for this lineage. Protein and/or mRNA expression of CD203c has also been found in solid tissues such as uterus or prostate. Basophils and mast cells are key producers of mediators that drive the onset of inflammatory responses, e.g., in allergy. Allergen challenge leads to a rapid up-regulation of activation markers such as CD203c or CD63. Due to its restricted expression pattern, CD203c is discussed as a specific marker to monitor the allergen-induced activation of basophils, e.g., in flow cytometric basophil activation tests of the peripheral blood. - Great Britain
TNF-α is a highly pleiotrophic cytokine that plays a role in immune inflammatory response. Intracellular signaling through TNF receptors may lead to apoptosis, cell activation, and/or cell proliferation. Whereas TNFR1 signaling is clearly involved in a number of pathological states (41), the role of TNFR2 in organ pathology is not widely established. Recently, a role for TNF-α in toxic and ischemic acute renal failure has been recognized (14, 16, 26, 44, 51). The mechanisms whereby TNF-α mediates acute renal failure are not clear. We used a clinically relevant model of acute renal failure, cisplatin nephrotoxicity, to investigate the TNF-α signaling pathways during acute renal injury. Several results are noteworthy.. First, we found that the expressions of both TNFR1 and TNFR2 are upregulated after cisplatin injection. This upregulation may serve to sensitize the kidney to the effects of TNF-α. In this regard, serum levels of TNF-α in cisplatin nephrotoxicity, although increased (44), are ...
Rat and mous. e Mrp3 share 88% and 89% similarity with human MRP3 at the protein level, respectively. Mrp3 is localized at the basolateral site of renal tubule cells, enterocytes, cholangiocytes and hepatocytes [1, 2]. Although basal expression of rat Mrp3 is low in the liver, it is induced in cholestatic conditions [3], Mrp2 deficiency [4, 5], and by certain drugs and microsomal enzyme inducers [6-10]. It is interesting to note, however, that levels of Mrp2 and Mrp3 are not always inversely correlated, as physiological Mrp2 deficiency in pregnant rats or downregulation of Mrp2 in obese Zucker rats do not cause upregulation of Mrp3 [11, 12]. Unlike in rat liver, Mrp3 has a constitutively high expression in mouse hepatocytes [13] which can be further induced with chemicals [14] but not by Mrp2 deficiency [15]. Within the kidney, MRP3 can be found in different cell types in humans versus rats. While rat Mrp3 is expressed in both the proximal and distal tubules [2], human MRP3 protein was ...
Figure: Induction of proinflammatory cytokines is attenuated in CX3CL1−/− mice expressing sFKN. TNFα and IL-1β concentrations were measured using standard ELISA techniques for VM lysates. a, TNFα concentrations were upregulated following MPTP administration (three-way ANOVA; F(1, 23) = 18.36, ★★★p , 0.001). Comparatively, CX3CL1−/− mice expressing sFKN in the SNpc had significantly lower concentrations of TNFα relative to mFKN (Tukeys HSD; ***p , 0.001) and GFP (Tukeys HSD; ###p , 0.001) expressing mice. There were no significant differences between sFKN and WT-MPTP (Tukeys HSD; p = 0.384) or mFKN and GFP (Tukeys HSD; p = 0.773). b, The IL-1β concentrations in the VM were significantly upregulated for mice exposed to MPTP (three-way ANOVA; F(1, 23) = 11.97, ★★★p = 0.002). Similar to the pattern of TNFα, IL-1β concentrations in CX3CL1−/− mice expressing sFKN were significantly blunted compared to both mFKN (Tukeys HSD; ***p = 0.001) and GFP (Tukeys HSD; ###p , ...
The precise role of CD26/DPP4 in tumor biology is unclear at this time. Preclinical studies have shown conflicting data with differential CD26/DPP4 expression and activity depending on the type of cancer. These studies suggest that it has a role as either a tumor suppressor or tumor activator depending on the tumor microenvironment and molecules with which CD26/DPP4 associates (1,3). However, since most of these studies involved in vitro assays, further investigations with in vivo experiments are needed to definitively establish the role of CD26/DPP4 in each cancer type.. Published studies have demonstrated that CD26/DPP4 plays a major role in the invasion and metastasis of selected cancers, and may be a novel therapeutic target (1,2,5,6). There are several suggested mechanisms for cancer metastasis involving the intrinsic peptidase activity of CD26/DPP4 and its subsequent chemokine regulation, as well as its ability to bind key molecules. For example, CD26/DPP4 can upregulate the expression of ...
X-MOL提供的期刊论文更新,Reproductive Biology and Endocrinology--MicroRNA-200b and microRNA-200c are up-regulated in PCOS granulosa cell and inhibit KGN cell proliferation via targeting PTEN,Tingting He; Yifei Sun; Yingchun Zhang; Shigang Zhao; Yanjun Zheng; Guimin Hao; Yuhua Shi
Similar to what has been previously observed following treatment of human leukemia cells with SAHA (38, 39, 43), treatment with LAQ824 also induced the hyperacetylation of histones H3 and H4 and increased expression of p21 in SKBR-3 and BT-474 cells. This is due to association of the promoter of p21 with acetylated histones in the nucleosomes (35). In contrast, increase in p27 levels following treatment with HDI is not due to transcriptional up-regulation. It may occur due to a post-transcriptional mechanism (35). Regardless, LAQ824-induced accumulation of p21 and p27 correlated with cytostasis as well as with induction of Bax conformational change, PARP cleavage activity of caspase-3, and apoptosis of SKBR-3 and BT-474 cells. Present studies also demonstrate for the first time that treatment with LAQ824 not only depletes the mRNA levels of Her-2 but also promotes its degradation by the proteasome. The mRNA levels of Her-2/neu declined markedly after short exposure intervals to LAQ824 as ...
The final results advise that up-regulation of MFGE8 is important for alveolar integrity and higher milk production in cows. In the existing examine 4 proteins