Protective Role of the Toll-Like Receptor 5 Agonist KMRC011 against Murine Colitis Induced by and Dextran Sulfate Sodium.

This study aimed to identify the therapeutic ability of a novel toll-like receptor (TLR) 5 agonist, KMRC011, on ulcerative colitis induced by and dextran sulfate sodium in a C57BL/6N mouse model. Ulcerative colitis was induced in the mice by the oral administration of 1% dextran sulfate sodium in sterile drinking water for seven days , followed by infection on the seventh day by intra-gastric administration (DSS-CT group). KMRC011 was administered intramuscularly at both 24 h and 15 min before (Treatment 1 group), and at both 15 min and 24 h after (Treatment 2 group) the infection.

A first-in-human study of KMRC011, a potential treatment for acute radiation syndrome, to explore tolerability, pharmacokinetics, and pharmacodynamics.

KMRC011 is a novel Toll-like receptor 5 agonist under development as a treatment for acute radiation syndrome (ARS). The aim of this first-in-human study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of a single intramuscular dose of KMRC011 in healthy subjects. A randomized, single-blind, placebo-controlled, single dose-escalation study was conducted with the starting dose of 5 μg.

IgLON5 Regulates the Adhesion and Differentiation of Myoblasts.

IgLON5 is a cell adhesion protein belonging to the immunoglobulin superfamily and has important cellular functions. The objective of this study was to determine the role played by IgLON5 during myogenesis. We found IgLON5 expression progressively increased in C2C12 myoblasts during transition from the adhesion to differentiation stage.

KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.

In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 μg/kg) after TBI.

Radioprotective effect of newly synthesized toll-like receptor 5 agonist, KMRC011, in mice exposed to total-body irradiation.

Exposure to ionizing radiation leads to severe damages in radiosensitive organs and induces acute radiation syndrome, including effects on the hematopoietic system and gastrointestinal system. In this study, the radioprotective ability of KMRC011, a novel toll-like receptor 5 (TLR5) agonist, was investigated in C57BL6/N mice exposed to lethal total-body gamma-irradiation. In a 30-day survival study, KMRC011-treated mice had a significantly improved survival rate compared with control after 11 Gy total-body irradiation (TBI), and it was found that the radioprotective activity of KMRC011 depended on its dosage and repeated treatment.

TLR5 binding and activation by KMRC011, a flagellin-derived radiation countermeasure.

Entolimod (CBLB502) is a flagellin-derived radiation countermeasure currently under clinical trial. Entolimod exerts radioprotective activity by directly interacting with TLR5, an innate immune receptor, using the conserved domains of flagellin. Entolimod was designed to contain an artificially introduced N-terminal region that is not related to drug effects and might trigger unexpected toxic immunogenic reactions in humans.

Repeated injection of KMRC011, a medical countermeasure for radiation, can cause adverse health effects in cynomolgus monkeys.

High-dose radiation-induced tissue damage is a major limiting factor in the medical application of nuclear technology. Herein, we tested 28-day repeated-dose toxicity of KMRC011, an agonist of toll-like receptor (TLR) 5, which is being developed as a medical countermeasure for radiation, using cynomolgus monkeys. KMRC011 (0.

Optimization of recombinant human platelet-derived growth factor-BB encapsulated in Poly (lactic-co-glycolic acid) microspheres for applications in wound healing.

Growth factors play multiple and critical roles in wound repair processes. Platelet-derived growth factor (PDGF) is a potent growth factor that is particularly important in the early inflammatory phase of wound healing. In order to extend the half-life of PDGF, polymeric encapsulation is used.

Comparative proteomic tissue analysis in patients with ossification of the posterior longitudinal ligament.

Objective: The ossification of the posterior longitudinal ligament (OPLL) involves the ligament that lines the posterior surface of the spinal vertebral bodies. Hormonal and metabolic factors as well as hereditary factors have been proposed to be involved in pathologic ligamentous OPLL. However, there are currently no definitive serological biomarkers for OPLL that might be used to achieve a more convenient and economic diagnosis.

Antibacterial properties of a pre-formulated recombinant phage endolysin, SAL-1.

To evaluate the phage endolysin SAL-1 as a therapeutic agent for Staphylococcus aureus infections, the in vitro and in vivo antibacterial properties of a pre-formulation containing recombinant SAL-1 as an active pharmaceutical ingredient were investigated. The stable pre-formulation (designated SAL200) uniquely included calcium ions and Poloxamer 188 as enhancing and stabilising ingredients, respectively. SAL-1 was successfully produced with no extraneous amino acids by decreasing the culture temperature and was highly purified using a two-step chromatography procedure consisting of ion exchange and hydrophobic interaction chromatography.

Activation of protease-activated receptor1 mediates induction of matrix metalloproteinase-9 by thrombin in rat primary astrocytes.

Thrombin plays an important role in diverse neurological processes such as proliferation, cell migration, differentiation and neuroinflammation. In this study, we investigated the effect of thrombin on matrix metalloprotease-9 (MMP-9) expression in rat primary astrocytes. Thrombin (1-10U/ml) induced a significant increase in MMP-9 activity as measured by gelatin zymography.

Differential regulation of matrix metalloproteinase-9 and tissue plasminogen activator activity by the cyclic-AMP system in lipopolysaccharide-stimulated rat primary astrocytes.

We investigated the effect of the cAMP system on lipopolysaccharide (LPS)-induced changes in the activity of matrix metalloproteinases (MMPs) and tissue plasminogen activator (tPA) in rat primary astrocytes. LPS stimulation increased MMP-9 and decreased tPA activity in rat primary astrocytes. Co-treatment with a cAMP analog, dibutyryl-cAMP (db-cAMP), or the cAMP elevating beta-adrenergic agonist, isoproterenol, concentration-dependently inhibited LPS-induced MMP-9 activity.

Characterization of ubiquitin C-terminal hydrolase 1 (YUH1) from Saccharomyces cerevisiae expressed in recombinant Escherichia coli.

The YUH1 gene coding for ubiquitin C-terminal hydrolase 1, a deubiquitinating enzyme, was cloned from the Saccharomyces cerevisiae genomic DNA and expressed in Escherichia coli. YUH1 was fused with the 6 histidine tag at the N-terminus (H6YUH1) or C-terminus (YUH1H6) and purified by an immobilized metal affinity chromatography with high purity. By using a fluorogenic substrate, Z-Arg-Leu-Arg-Gly-Gly-AMC, the deubiquitinating activities for H6YUH1 (1.

Role of p38 MAPK on the down-regulation of matrix metalloproteinase-9 expression in rat astrocytes.

In spite of their pathophysiological importance in neuro-inflammatory diseases, little is known about the signal transduction pathways that lead to the induction of matrix metalloproteinases (MMPs) in the central nervous system. We reported previously that lipopolysaccharide (LPS) induced MMP-9 expression through ERK1/2 pathway in rat primary astrocytes (Glia 41:15-24, 2003). Here, we investigated the role of other MAPK pathways, including p38 and JNK/SAPK, on the regulation of MMP-9 expression in LPS-stimulated rat primary astrocytes.

Down-regulation of matrix metalloproteinase-9 expression by nitric oxide in lipopolysaccharide-stimulated rat primary astrocytes.

Immunologically activated astrocytes over-express matrix metalloproteinase-9 (MMP-9) and nitric oxide (NO). Because they have both beneficial and detrimental effects on the pathophyiological outcomes of several neurological diseases, their expression should be tightly regulated in the CNS. NO can modify the activity of other proteins either by directly modifying protein structure or regulating the expression of target proteins.

Comparative analysis of serum proteomes to discover biomarkers for ossification of the posterior longitudinal ligament.

Study Design: Serum proteomes from normal subjects and the patients with ossification of the posterior longitudinal ligament (OPLL) were analyzed by using proteomics.

Objectives: To identify novel serologic biomarkers for diagnosing OPLL.

Summary Of Background Data: OPLL can compress the spinal cord, and special planning is required for surgeries that are done from the front of the cervical spine.

Glucose deprivation increases hydrogen peroxide level in immunostimulated rat primary astrocytes.

Activated astrocytes produce a large amount of bioactive molecules, including reactive oxygen and nitrogen species. Astrocytes are in general resistant to those reactive species. However, we previously reported that immunostimulated astrocytes became highly vulnerable to metabolic insults, such as glucose deprivation.

Induction of matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide-stimulated primary astrocytes is mediated by extracellular signal-regulated protein kinase 1/2 (Erk1/2).

In the present study, we investigated whether the activation of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (Erk1/2) are involved in the induction of MMP-9 in lipopolysaccharide (LPS)-stimulated primary astrocytes. The expression of MMP-9 but not MMP-2 was increased by LPS. LPS treatment induced activation of Erk1/2 within 30 min, which was dose-dependently inhibited by PD98059, a specific inhibitor of the Erk kinase (MEK).

Platycodin D and D3 increase airway mucin release in vivo and in vitro in rats and hamsters.

The root of Platycodon grandiflorum has been widely used for the treatment of various chronic inflammatory diseases including airway disease in oriental medicine. The root extract of the plant has been known to be effective in the expectoration of sputum or mucus, thereby improving airway respiratory function and preventing secondary airway inflammation. In this study, we investigated the effect of platycodin D and D3, the saponin components that are anti-inflammatory components in Platycodon grandiflorum.