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#32770866   2020/08/08 To Up

Expression of discoidin domain receptor 1 and E-cadherin in epidermis affects melanocyte behavior in rhododendrol-induced leukoderma mouse model.

Vitiligo is a depigmentation disease characterized by gradual loss of melanin and melanocytes from the epidermis. The mechanism of melanocyte loss is not yet known. In this report, we showed that the expression of discoidin domain receptor 1 and E-cadherin, known adhesion molecules, was variable or absent in the epidermis of rhododendrol-induced leukoderma (RDIL) mice during the depigmentation process. Our findings suggest that melanocyte damage by rhododendrol promotes reduction of adhesion molecules not only in melanocytes but also in keratinocytes, and this is associated with the detachment of melanocytes from the basal layer.
Yuko Abe, Yutaka Hozumi, Ken Okamura, Tamio Suzuki

1330 related Products with: Expression of discoidin domain receptor 1 and E-cadherin in epidermis affects melanocyte behavior in rhododendrol-induced leukoderma mouse model.

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#32770858   2020/08/08 To Up

Updated information on new coronavirus disease 2019 occurrence, drugs, and prediction of a potential receptor.

The new coronavirus (COVID-19) was first reported in Wuhan in China, on 31 December 2019. COVID-19 is a new virus from the family of coronaviruses that can cause symptoms ranging from a simple cold to pneumonia. The virus is thought to bind to the angiotensin-converting enzyme 2, as a well-known mechanism to enter the cell. It then transfers its DNA to the host in which the virus replicates the DNA. The viral infection leads to severe lack of oxygen, lung oxidative stress because of reactive oxygen species generation, and overactivation of the immune system by activating immune mediators. The purpose of this review is to elaborate on the more precise mechanism(s) to manage the treatment of the disease. Regarding the mechanisms of the virus action, the suggested pharmacological and nutritional regimens have been described.
Forouzan Khodaei, Anam Ahsan, Mostafa Chamanifard, Mohammad Javad Zamiri, Mohammad Mehdi Ommati

1610 related Products with: Updated information on new coronavirus disease 2019 occurrence, drugs, and prediction of a potential receptor.

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#32770836   2020/08/08 To Up

Immune-mobilising monoclonal T cell receptors mediate specific and rapid elimination of Hepatitis B-infected cells.

New therapies for chronic HBV infection are urgently needed due to viral integration, persistence of viral antigen expression, inadequate HBV-specific immune responses and treatment regimens that require life-long adherence to suppress the virus. Immune mobilising monoclonal T cell receptors Against Virus (ImmTAV ) molecules represent a novel therapeutic strategy combining an affinity-enhanced T cell receptor with an anti-CD3 T cell-activating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virus-derived peptides presented by human leukocyte antigen (HLA).
Joannah R Fergusson, Zoë Wallace, Mary M Connolly, Amanda P Woon, Richard J Suckling, Dominic W Hine, Claire Barber, Wilawan Bunjobpol, Beak-San Choi, Sara Crespillo, Marcin Dembek, Nele Dieckmann, Jose Donoso, Luis F Godinho, Tressan Grant, Dawn Howe, Michelle L McCully, Carole Perot, Anshuk Sarkar, Florian U Seifert, Praveen K Singh, Kerstin A Stegmann, Bethany Turner, Anil Verma, Andrew Walker, Sarah Leonard, Mala K Maini, Katrin Wiederhold, Lucy Dorrell, Ruth Simmons, Andrew Knox

1807 related Products with: Immune-mobilising monoclonal T cell receptors mediate specific and rapid elimination of Hepatitis B-infected cells.

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#32770831   2020/08/08 To Up

Cannabidivarin for HIV-associated neuropathic pain - a randomized, blinded, controlled clinical trial.

The human immunodeficiency virus (HIV) remains a major burden to the health care system and neuropathic pain is the most common neurological complication of HIV infection. Since current treatment strategies often lack satisfying pain relief, cannabinoids are discussed as a new option. We investigated cannabidivarin as treatment for HIV-associated neuropathic pain. We conducted a randomized, double-blind, placebo-controlled cross-over study. Patients underwent two successive treatment phases (4 weeks each) and were treated with cannabidivarin (400mg/d) or placebo in a randomized order. A 3-week wash-out phase was designed to eliminate potential carry-over effects. Patients were followed up for 3 weeks after the end of the second treatment phase. The primary endpoint was pain intensity on an 11-point numeric rating scale, recorded in a diary. Secondary endpoints were additional pain medication, pain characteristics and quality of life. We included 32 patients. The mean pain intensity under cannabidivarin was 0.62 points higher compared to placebo (p=0.16; 95% CI -0.27 to 1.51). Cannabidivarin did not influence the amount of additional pain medication, pain characteristics or quality of life. The incidence of adverse events was similar during both treatments. No suspected unexpected adverse reactions occurred during either treatment. Cannabidivarin was safe but failed to reduce neuropathic pain in HIV-patients. This may be explained by a lack of cannabinoid receptor activation, as indicated by preclinical experiments. Although a larger patient number might be desirable, we would not expect a change in the conclusions since the present differences are far from statistical significance. Therefore, we would currently not consider CBDV as a clinically meaningful treatment option for neuropathic pain.
Luca Eibach, Simone Scheffel, Madeleine Cardebring, Marie Lettau, M Özgür Celik, Andreas Morguet, Robert Roehle, Christoph Stein

2840 related Products with: Cannabidivarin for HIV-associated neuropathic pain - a randomized, blinded, controlled clinical trial.

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#32770720   2020/08/08 To Up

Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181).

Budigalimab (ABBV-181) is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD-1) receptor, currently in phase 1 clinical trials. The safety, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and budigalimab dose selection from monotherapy dose escalation and multi-histology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every two weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from weight-based dosing in the escalation phase, based on which patients in the multi-histology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W). Immune related adverse events were reported in 11/59 (18.6%) patients, of which 1/59 (1.7%) was considered Grade ≥ 3 and the safety profile of budigalimab was consistent with other PD-1 targeting agents. No treatment-related Grade 5 adverse events were reported. Four responses per RECIST (v1.1) were reported in the dose escalation cohort and none in the multi-histology expansion cohort. PK of budigalimab was approximately dose proportional and sustained > 99% peripheral PD-1 receptor saturation was observed by 2 hours post dosing, across doses. PK/PD and safety profiles were comparable between Japanese and Western patients, and exposure-safety analyses did not indicate any trends. Observed PK and PD-1 receptor saturation were consistent with model predictions for flat doses and less frequent regimens, validating the early application of PK modeling and PK/PD assessments to inform the recommended dose and regimen, following dose escalation.
John Powderly, Alexander Spira, Shunsuke Kondo, Toshihiko Doi, Jason J Luke, Drew Rasco, Bo Gao, Minna Tanner, Philippe A Cassier, Anas Gazzah, Antoine Italiano, Diego Tosi, Daniel E Afar, Apurvasena Parikh, Benjamin Engelhardt, Stefan Englert, Stacie L Lambert, Sreeneeranj Kasichayanula, Sven Mensing, Rajeev Menon, Gregory Vosganian, Anthony Tolcher

1140 related Products with: Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181).

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#32770674   2020/08/08 To Up

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia.

Autosomal-dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1,985 controls. 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (p<.05) and healthy controls (p<.001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL-C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a 6-SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients. This article is protected by copyright. All rights reserved.
Lorenz Rieck, Frieda Bardey, Thomas Grenkowitz, Lars Bertram, Johannes Helmuth, Claudia Mischung, Joachim Spranger, Elisabeth Steinhagen-Thiessen, Thomas Bobbert, Ursula Kassner, Ilja Demuth

1445 related Products with: Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia.



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#32770660   2020/08/07 To Up

Comment on: Nrf2 regulates interferon receptor expression and alters macrophage polarization in lupus.

Systemic lupus erythematosis (SLE) is an inflammatory autoimmune disease with multiple organs, systems damage. To date, the clear pathogenesis of SLE has not been fully clarified. However, genetics, environmental factors and dysregulated immunity were related to onset of this complex disease.
Wang-Dong Xu, An-Fang Huang

1151 related Products with: Comment on: Nrf2 regulates interferon receptor expression and alters macrophage polarization in lupus.

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#32770654   2020/08/08 To Up

CAR T-cell therapy-related neurotoxicity in paediatric acute lymphocytic leukaemia.

The advent of chimeric antigen receptor (CAR) T-cell therapy has created a paradigm shift in the management of patients with refractory B-cell acute lymphocytic leukaemia (ALL). The aim of this study is to correlate imaging findings of CAR T-cell therapy related neurotoxicity with clinical course and eventual clinical outcome, with the hope that it will bring us a step closer to the identification of potential imaging biomarkers that may allow more accurate prognostication and risk stratification of patients.
Ai Peng Tan

1751 related Products with: CAR T-cell therapy-related neurotoxicity in paediatric acute lymphocytic leukaemia.



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