Targeting of oxidized Macrophage Migration Inhibitory Factor (oxMIF) with antibody ON104 attenuates the severity of glomerulonephritis.

The oxidized form of Macrophage Migration Inhibitory Factor (oxMIF) has been identified as the disease-related isoform of MIF, exerting pathological functions in inflamed tissue. In this study, we aimed to explore the in vivo effects of the neutralizing anti-oxMIF antibody ON104 in a rat model of crescentic glomerulonephritis (CGN), to better understand its disease modifying activities. WKY rats received a single intravenous injection of a rabbit nephrotoxic serum (NTS), targeting rat glomerular basement membrane to induce CGN.

The newly engineered monoclonal antibody ON104, targeting the oxidized Macrophage Migration Inhibitory Factor (oxMIF), ameliorates clinical and histopathological signs of collagen-induced arthritis.

Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine that emerged as a pivotal regulator in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA). MIF occurs in two immunologically distinct conformational isoforms, indicated as reduced (redMIF) and oxidized MIF (oxMIF) where the latter exerts disease-related activities. In this study we demonstrate the presence of circulating oxMIF in RA patients and investigate the in vivo effects of an oxMIF-neutralizing antibody in a murine model of RA.

Preclinical Data on the -Specific Endolysin PM-477 Indicate Its Potential to Improve the Treatment of Bacterial Vaginosis through Enhanced Biofilm Removal and Avoidance of Resistance.

Antibiotics are the mainstay of therapy for bacterial vaginosis (BV). However, the rate of treatment failure in patients with recurrent BV is about 50%. Herein, we investigated potential mechanisms of therapy failure, including the propensity of resistance formation and biofilm activity of metronidazole (MDZ), clindamycin (CLI), and PM-477, a novel investigational candidate that is a genetically engineered endolysin with specificity for bacteria of the genus .

Optimization of Propidium Monoazide qPCR (Viability-qPCR) to Quantify the Killing by the -Specific Endolysin PM-477, Directly in Vaginal Samples from Women with Bacterial Vaginosis.

Quantification of the number of living cells in biofilm or after eradication treatments of biofilm, is problematic for different reasons. We assessed the performance of pre-treatment of DNA, planktonic cells and ex vivo vaginal biofilms of with propidium monoazide (PMAxx) to prevent qPCR-based amplification of DNA from killed cells (viability-qPCR). Standard PMAxx treatment did not completely inactivate free DNA and did not affect living cells.

Engineered Phage Endolysin Eliminates Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo.

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different species.

The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden.CETP mice.

Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden.

Peptide-based vaccination against OPN integrin binding sites does not improve cardio-metabolic disease in mice.

Obesity causes insulin resistance via a chronic low-grade inflammation. This inflammation is characterized by elevated pro-inflammatory markers and macrophage accumulation in the adipose tissue (AT). AT inflammation is a key factor causing insulin resistance and thus type 2 diabetes, both linked to atherosclerotic cardiovascular disease.

Active immunization against complement factor C5a: a new therapeutic approach for Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by neuronal loss due to amyloid beta aggregations, neurofibrillary tangles, and prominent neuroinflammation. Recently, interference with neuroinflammation as a new therapeutic approach for AD treatment gained great interest. Microglia cells, one of the major contributors in neuroinflammation, are activated in response to misfolded proteins such as amyloid β and cell debris leading to a sustained release of pro-inflammatory mediators.

The Pan-AC assay: a single-reaction real-time PCR test for quantitative detection of a broad range of Aspergillus and Candida species.

In view of the growing incidence and the high mortality of invasive aspergillosis and candidiasis, adequate diagnostic techniques permitting timely onset of treatment are of paramount importance. More than 90 % of all invasive fungal infections in immunocompromised individuals can be attributed to Candida and Aspergillus species. To date, standardized techniques permitting rapid, sensitive and, no less importantly, economic screening for the clinically most relevant fungi are lacking.

Myristoylation of human LanC-like protein 2 (LANCL2) is essential for the interaction with the plasma membrane and the increase in cellular sensitivity to adriamycin.

Human LANCL2, also known as Testis-specific Adriamycin Sensitivity Protein (TASP), is a member of the highly conserved and widely distributed lanthionine synthetase component C-like (LANCL) protein family. Expression studies of tagged LANCL2 revealed the major localization to the plasma membrane, juxta-nuclear vesicles, and the nucleus, in contrast to the homologue LANCL1 that was mainly found in the cytosol and nucleus. We identified the unique N-terminus of LANCL2 to function as the membrane anchor and characterized the relevant N-terminal myristoylation and a basic phosphatidylinositol phosphate-binding site.