Fig. 5. Perturbations of AHR-STUB1-TF axis normalize the hyperthrombotic uremic phenotype without altering the bleeding risk. Perturbations of AHR-STUB1-TF.

Slides:

Advertisements

Similar presentations

Fig. 2. Effects of AZD4785 on proliferation and MAPK pathway signaling in KRAS mutant and wild-type cancer cells in vitro. Effects of AZD4785 on proliferation.

Advertisements

Fig. 1. IL-6 is associated with resistance to EGFR TKIs and is induced by stress hormones. IL-6 is associated with resistance to EGFR TKIs and is induced.

Fig. 6. AZD6738 induces DNA damage and apoptosis and exhibits antitumor efficacy in xenograft models of high-risk medulloblastoma and neuroblastoma. AZD6738.

Differentiation of AZD4785 from MAPK pathway inhibitors in vitro

Fig. 5. Blocking LTB4 during initial lymphangiogenesis period abrogates the therapeutic benefit of LTB4 antagonism. Blocking LTB4 during initial lymphangiogenesis.

Fig. 5. Correlation between CD34+CD45RA−CD90+ cell dose, engraftment success, and onset of neutrophil/platelet recovery in nonhuman primates. Correlation.

Fig. 3. A dynamic STUB1-TF interaction depends on the uremic status.

Fig. 2. Mechanism of PD-L1 down-regulation in NOD HSPCs.

Fig. 5. Correlation of tail and long bone growth velocities with Cxm serum concentrations in mice. Correlation of tail and long bone growth velocities.

Neutrophil aggregation is selectively induced by PS+ platelets

Fig. 5 Maraba induces antitumor T cell immunity.

In vivo prophylactic and therapeutic efficacy of C12G6 in mice

Fig. 3. Obese IFN-γ−/− mice develop accelerated NAFLD with fibrosis.

Fig. 6. Treatment with a DLK inhibitor is neuroprotective and reverses stress-induced gene expression changes. Treatment with a DLK inhibitor is neuroprotective.

Synergistic effect of S63845 with lapatinib, trastuzumab, or docetaxel

Fig. 8. In vivo suppression of MM by CMLD

Fig. 1. NASH and fibrosis develop late in mice fed an HFD.

Fig. 8. mRIPO elicits neutrophil influx followed by DC and T cell infiltration into tumors. mRIPO elicits neutrophil influx followed by DC and T cell infiltration.

Fig. 4 Infection-induced CLV dysfunction is associated with decreased LMC coverage. Infection-induced CLV dysfunction is associated with decreased LMC.

Bio-AMS enhances the activity of rifampicin and ethambutol in vitro

Fig. 3. Paclitaxel promotes TMEM-dependent vascular permeability, cancer cell dissemination, and metastasis in breast cancer. Paclitaxel promotes TMEM-dependent.

Fig. 5. Pharmacological JAK2 inhibition in vivo abrogates tumor-initiating potential after chemotherapy. Pharmacological JAK2 inhibition in vivo abrogates.

Fig. 3. Fc fusion GDF15 molecules improve metabolic parameters in obese mice and obese cynomolgus monkeys. Fc fusion GDF15 molecules improve metabolic.

Fig. 8. Therapeutic effects of the transplantation of hiPSC-EPO–producing cells on renal anemia in adenine-treated mice. Therapeutic effects of the transplantation.

Fig. 4. Antitumor efficacy of ERY974 against various cancer types.

Fig. 4 CXCL4 potentiates TLR8-mediated activation of SSc pDCs.

Fig. 1. IS mediates a hyperthrombotic uremic phenotype in an AHR-dependent manner across CKD stages. IS mediates a hyperthrombotic uremic phenotype in.

Fig. 7 Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors. Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors.

Fig. 2. Effects of SFN in mouse hepatocytes and in rat models of diet-induced glucose intolerance. Effects of SFN in mouse hepatocytes and in rat models.

Type 1 immunity drives metabolic disease but protects against NAFLD

Fig. 4. MATE1 transcription in RCC.

Fig. 7 pDCs are critical for the maintenance of skin fibrosis and for the presence of CXCL4 in the skin. pDCs are critical for the maintenance of skin.

Fig. 6. Apoptotic MSCs exert in vivo immunosuppression in a TH2-type inflammation model in the absence of cytotoxic cells. Apoptotic MSCs exert in vivo.

Fig. 8 TLR8 exacerbates disease in the BLM-induced fibrosis model.

Fig. 6 pDCs infiltrate the skin of BLM-treated mice, and their depletion attenuates skin fibrosis. pDCs infiltrate the skin of BLM-treated mice, and their.

Fig. 2. RT-QuIC testing of sCJD and vCJD brain and skin samples.

Fig. 5. Accelerated NASH-driven fibrogenesis in obese IFN-γ−/− mice is characterized by severe eosinophilic inflammation during TGF-β blockade. Accelerated.

Fig. 7 BRD0705 impairs colony formation in AML cell lines and patient cells and shows in vivo efficacy in multiple AML mouse models. BRD0705 impairs colony.

Fig. 4 DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft tumor models. DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft.

Fig. 2. Resistance to S63845-induced apoptosis through loss of BAK or elevated BCL-XL. Resistance to S63845-induced apoptosis through loss of BAK or elevated.

Fig. 3. The effects of DCA on hemodynamic and functional end points and their association with genetic factors (variants of the SIRT3 and UCP2 genes) that.

Fig. 2. STUB1 destabilizes and ubiquitinates TF and mediates TF regulation by AHR. STUB1 destabilizes and ubiquitinates TF and mediates TF regulation by.

Fig. 2 Paralog-selective inhibitors of GSK3α and GSK3β were designed and characterized. Paralog-selective inhibitors of GSK3α and GSK3β were designed and.

Fig. 7. ApoMSCs exert immunosuppressive activity in GvHD and elicit IDO in engulfing recipient phagocytes. ApoMSCs exert immunosuppressive activity in.

Fig. 3. β-AR signaling induces IL-6 in NSCLC cells via activation of PKC and CREB. β-AR signaling induces IL-6 in NSCLC cells via activation of PKC and.

Fig. 4. Improved tumor response to docetaxel in TNBC and trastuzumab in HER2-amplified PDX models with the addition of S Improved tumor response.

Fig. 7. Therapeutic effects of hiPSC-EPO protein on renal anemia in adenine-treated mice. Therapeutic effects of hiPSC-EPO protein on renal anemia in adenine-treated.

Stroke induces atheroprogression via the RAGE-signaling pathway

Fig. 1 Effect of preinfection β7Hi CD45RA−CD4+ T cell frequency on HIV acquisition risk in CAPRISA 004 study. Effect of preinfection β7Hi CD45RA−CD4+ T.

Fig. 2. IL-2/rapamycin–expanded T cells express homing receptors to traffic to lymphoma sites and are resistant to SN-38 toxicity. IL-2/rapamycin–expanded.

Fig. 3. TKI sensitivity assessed by the MANO method.

Fig. 4. The effect of single-dose rozanolixizumab on the concentration of IgG subtypes in healthy subjects. The effect of single-dose rozanolixizumab on.

Fig. 2. CD31 provides robust NP targeting in vitro but slow kinetics.

CD facilitates RCT in vivo and promotes urinary cholesterol excretion

Fig. 3 Agonists of innate immunity are effective only when released locally from the hydrogel. Agonists of innate immunity are effective only when released.

Fig. 4. Local application of FR provides prolonged protection against Gq-dependent airway constriction in normal and OVA-sensitized mice in vivo. Local.

Fig. 2. Cellular response to FolamiRs in vitro.

Fig. 5 Extended local release of R848 increases the number of innate and adaptive antitumor immune cells and cytokines. Extended local release of R848.

Fig. 5 HDAC inhibition blocks age-dependent diastolic dysfunction.

Fig. 5 Treatment with an OX40 agonist antibody of 3-week-old HBVtgRag−/− mice or mice with chronic HBV disease results in an altered immune response to.

Fig. 4. Clearance of 12-mer-1 from a nonhuman primate model.

Fig. 3. Phenotypic characterization of FM2.5.

Fig. 2. CD treatment facilitates regression of murine atherosclerosis.

Fig. 1. MSCs undergo in vivo apoptosis after infusion without affecting immunosuppression. MSCs undergo in vivo apoptosis after infusion without affecting.

GLP-1 and gastrin combination therapy restores normoglycemia in NOD mice. GLP-1 and gastrin combination therapy restores normoglycemia in NOD mice. Beginning.

BMS blocks functional responses in primary immune cells driven by IFNα

by Samuel J. Taylor, Johanna M. Duyvestyn, Samantha A. Dagger, Emma J

Fig. 1. The HCN channel blocker ivabradine (IVA) is analgesic in a mouse model of type 1 diabetes. The HCN channel blocker ivabradine (IVA) is analgesic.

Fig. 3. Human liver tissue seed graft function.

Effect of MZ treatment on lung colony formation in an experimental metastasis. Effect of MZ treatment on lung colony formation in an experimental metastasis.

Presentation transcript:

Fig. 5. Perturbations of AHR-STUB1-TF axis normalize the hyperthrombotic uremic phenotype without altering the bleeding risk. Perturbations of AHR-STUB1-TF axis normalize the hyperthrombotic uremic phenotype without altering the bleeding risk. (A) The experimental design assessing the effect of YL-109 on the IS-specific uremic thrombosis model. A dose of heparin that increases activated partial thromboplastin time (aPTT) to the therapeutic range in mice (35) was administered 2 hours before the procedure. IP, intraperitoneal; PO, per os. (B) Representative traces of carotid artery blood flow showing TtO (arrow) in different groups. (C) An average TtO from each group of animals from three independent experiments is shown. The numbers of animals used include probenecid (n = 9), probenecid + IS (n = 12), probenecid + IS + YL-109 (n = 8), and probenecid + IS + heparin (n = 6). No difference in TtO was observed between probenecid and probenecid + IS + YL-109 (P = 0.65). Heparin significantly prolonged TtO compared to both IS and probenecid control groups (P = 0.021). Data are shown as means ± SD. (D) Mean normalized TF and STUB1 expression in the aortae of five mice injected with IS with or without YL-109 is shown. Student’s t test was performed. Data are shown as means ± SD. (E) Changes in TF expression in the individual aortae of IS + YL-109–treated animals and their respective TtO are shown. A Spearman correlation analysis was performed. (F) IS concentrations in the blood of mice exposed to 0.25% adenine diet for 2 weeks and animals on regular chow (control) (n = 5 per group). Data are shown as means ± SD. (G) An average TtO in control (regular diet) and adenine-induced CKD mice with AHR inhibitor (CH223191) or STUB1 enhancer (YL-109) (n = 5 per group) is shown. #P value compares the adenine and control groups. *P value compares CH223191 and YL-109 groups with the adenine group. Data are shown as means ± SEM. (H) Average tail vein bleeding times for each group (n = 5 per group). Data are shown as means ± SD. (I) Differences in the average tail vein bleeding times (y axis) between probenecid control (non-CKD) and other groups (CKD). The solid line represents the average bleeding time of the control group, and the dotted lines represent two SDs of bleeding time from the control group. The shaded areas are the regions beyond 2 SD. Moshe Shashar et al., Sci Transl Med 2017;9:eaam8475 Published by AAAS