Publications by authors named "Sven Michel"

Early characterization of the immunostimulatory potential of therapeutic antisense oligonucleotides (ASOs) is crucial. At present, little is known about the toll-like receptor 9 (TLR9)-mediated immunostimulatory potential of third-generation locked nucleic acid (LNA)-modified ASOs. In this study, we have systematically investigated the TLR9-activating potential of LNA-modified oligonucleotides using different mouse and human cell culture systems.

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Background: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection.

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Article Synopsis
  • The study aimed to explore how different outcome measures (symmetry-based and performance-based) relate to each other in patients undergoing total hip arthroplasty (THA) due to end-stage hip osteoarthritis.
  • It involved 24 patients assessed before surgery and at multiple points post-op using various functional tests, with improvements noted by the 10th week post-surgery.
  • The results showed no strong correlations between the different types of measures, indicating that each measure provides unique information and highlighting the need for more clarity on the role of symmetry in evaluating function after THA.
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Antisense oligonucleotides (ASOs) are a novel therapeutic strategy that targets a specific gene and suppresses its expression. The cryopyrin-associated periodic syndromes (CAPS) are a spectrum of autoinflammatory diseases characterized by systemic and tissue inflammation that is caused by heterozygous gain-of-function mutations in the nucleotide-binding and oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) gene. The aim of this study was to investigate the efficacy of an Nlrp3-specific ASO treatment in CAPS.

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Background: Although immune checkpoint inhibitors have been a breakthrough in clinical oncology, these therapies fail to produce durable responses in a significant fraction of patients. This lack of long-term efficacy may be due to a poor pre-existing network linking innate and adaptive immunity. Here, we present an antisense oligonucleotide (ASO)-based strategy that dually targets toll-like receptor 9 (TLR9) and programmed cell death ligand 1 (PD-L1), aiming to overcome resistance to anti-PD-L1 monoclonal therapy.

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A randomized crossover trial was designed to investigate the influence of muscle activation and strength on functional stability/control of the knee joint, to determine whether bilateral imbalances still occur six months after successful anterior cruciate ligament reconstruction (ACLR), and to analyze whether the use of orthotic devices changes the activity onset of these muscles. Furthermore, conclusions on the feedforward and feedback mechanisms are highlighted. Therefore, twenty-eight patients will take part in a modified Back in Action (BIA) test battery at an average of six months after a primary unilateral ACLR, which used an autologous ipsilateral semitendinosus tendon graft.

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Purpose: The aim of this study was to assess the reproducibility and reliability of the KomPAN questionnaire among two groups of university students from Germany and Slovakia.

Methods: A total of 422 individuals (mean age 21.4 years, SD 4.

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Angiopoietin-like 4 (ANGPTL4) is an important regulator of plasma triglyceride (TG) levels and an attractive pharmacological target for lowering plasma lipids and reducing cardiovascular risk. Here, we aimed to study the efficacy and safety of silencing ANGPTL4 in the livers of mice using hepatocyte-targeting GalNAc-conjugated antisense oligonucleotides (ASOs). Compared with injections with negative control ASO, four injections of two different doses of ANGPTL4 ASO over 2 weeks markedly downregulated ANGPTL4 levels in liver and adipose tissue, which was associated with significantly higher adipose LPL activity and lower plasma TGs in fed and fasted mice, as well as lower plasma glucose levels in fed mice.

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Background: Maladaptive endoplasmic reticulum stress signaling in diabetic kidney disease (DKD) is linked to increased glomerular and tubular expression of the cell-death-promoting transcription factor C/EBP homologous protein (CHOP). Here, we determined whether locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) targeting CHOP ameliorate experimental DKD.

Methods: We determined the efficacy of CHOP-ASO in the early and late stages of experimental DKD (in 8- or 16-week-old db/db mice, respectively) alone or with an angiotensin-converting enzyme inhibitor (ACEi), after an in vivo dose-escalation study.

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Locked nucleic acid-modified antisense oligonucleotides (ASOs) can achieve strongly different degrees of target knockdown despite having similar biophysical properties and 100% homology with their target. The determinants for this observation remain largely unknown. We used multi-specific ASOs that have 100% sequence complementarity with a common target () and a different number of diverse targets and investigated their effect on gene expression in a cell line by RNA-sequencing.

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Purpose: Standardized outcome measures are crucial for the evaluation of different treatment and rehabilitation regimes in patients after total knee arthroplasty (TKA). Performance-based measures are necessary to capture different aspects of physical function. High reliability and agreement of five performance-based measures were hypothesized to differentiate between measurement error and change in test performance.

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Background: The field of antisense oligonucleotide therapeutics is rapidly growing and in addition to small molecules and therapeutic antibodies, oligonucleotide-based gene expression modifiers have been developed as fully accepted therapeutics. Antisense oligonucleotides are designed to modify gene expression of their specific target genes. However, as their effect relies on Watson-Crick base pairing, they could also bind to other unintended complementary RNAs showing sufficient sequence homology, which in turn could lead to off-target effects.

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The eating habits of students differ significantly from those recommended by health practitioners. The aim of this study was to find differences related to diet quality and knowledge on nutrition among Polish, German, and Slovakian students as well as to examine which factors differentiate the diet quality of students from these three countries. The study was conducted on a group of 394 university students from Poland, Germany, and Slovakia.

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Colorectal and lung cancers account for one-third of all cancer-related deaths worldwide. Previous studies suggested that metadherin (MTDH) is involved in the development of colorectal and lung cancers. However, how MTDH regulates the pathogenesis of these cancers remains largely unknown.

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The adenosine axis contributes to the suppression of antitumor immune responses. The ectonucleotidase CD39 degrades extracellular adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is degraded to adenosine by CD73. Adenosine binds to, e.

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Introduction: There is a lack of harmonising measures for clinical trials on total joint replacement (TJR) that would allow for results from TJR studies to be compared or pooled. The Outcome Measures in Rheumatology (OMERACT) TJR core domain set is already endorsed among patients and physicians in the USA and Australia. Physiotherapists use different types of measurements compared to orthopaedic surgeons while both make substantial contributions to research in the field of TJR.

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Tumors can utilize a diverse repertoire of immunosuppressive mechanisms to evade attack by the immune system. Despite promising success with blockade of immune checkpoints like PD-1 the majority of patients does not respond to current immunotherapies. The degradation of tryptophan into immunosuppressive kynurenine is an important immunosuppressive pathway.

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Ebola virus is the causative agent of Ebola virus disease, a severe, often fatal illness in humans. So far, there are no US Food and Drug Administration (FDA)-approved therapeutics directed against Ebola virus. Here, we selected the host factor Niemann-Pick C1 (NPC1), which has been shown to be essential for Ebola virus entry into host cytoplasm, as a therapeutic target for suppression by locked nucleic acid-modified antisense oligonucleotides.

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Background: Neuropeptide S Receptor 1 ( NPSR1) and Retinoid Acid Receptor-Related Orphan Receptor Alpha (RORA ) interact biologically, are both known candidate genes for asthma, and are involved in controlling circadian rhythm. Thus, we assessed (1) whether interactions between RORA and NPSR1 specifically affect the nocturnal asthma phenotype and (2) how this may differ from other asthma phenotypes.

Methods: Interaction effects between 24 single-nucleotide polymorphisms (SNPs) in RORA and 35 SNPs in NPSR1 on asthma and nocturnal asthma symptoms were determined in 1432 subjects (763 asthmatics [192 with nocturnal asthma symptoms]; 669 controls) from the Multicenter Asthma Genetic in Childhood/International Study of Asthma and Allergies in Childhood studies.

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Understanding the intrinsic mediators that render CD8 T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of tumor-reactive CD8 T cells. Chop expression is increased in tumor-infiltrating CD8 T cells, which correlates with poor clinical outcome in ovarian cancer patients.

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Background: Cancer cells are known to develop mechanisms to circumvent effective anti-tumor immunity. The two ectonucleotidases CD39 and CD73 are promising drug targets, as they act in concert to convert extracellular immune-stimulating ATP to adenosine. CD39 is expressed by different immune cell populations as well as cancer cells of different tumor types and supports the tumor in escaping immune recognition and destruction.

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The purpose of this study was to investigate if there are still deficits in muscle mass or strength capabilities in elite judo athletes with a history of anterior cruciate ligament reconstruction (ACLR) after their return to the sport. Therefore, bioimpedance analysis, 3D-laser thigh circumference measurement and isokinetic dynamometry in a closed kinetic chain were used. The side-to-side differences were investigated in a group of judo athletes 5 years after ACLR (n=17) and compared with a group of healthy judo athletes (n=27).

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Background: The symptomatic reduction of exercise-induced delayed-onset muscle soreness (DOMS) is of great interest in the fields of Sports Medicine and Physical Therapy. At this time, few therapeutic interventions have proven their effectiveness. One of the most promising interventions is compression therapy.

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Background: Infections with human rhinoviruses (RVs) are responsible for millions of common cold episodes and the majority of asthma exacerbations, especially in childhood. No drugs specifically targeting RVs are available.

Objective: We sought to identify specific anti-RV molecules based on DNAzyme technology as candidates to a clinical study.

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