Abstract Interleukin (IL)-8, a prototypic human chemokine, was detected more than decade ago as the founding member of chemokine superfamily. One most remarkable properties IL-8 is variation its expression levels. In healthy tissues, barely detectable, but it rapidly induced by ten- to 100-fold in response proinflammatory cytokines such tumor necrosis factor or IL-1, bacterial viral products, and cellular stress. Recently, significant advances understanding signaling pathways, which...

Bone morphogenetic protein 2 (BMP‐2) plays a decisive role during bone regeneration and repair as well various stages of embryonal development. A cDNA encoding mature human BMP‐2 could be efficiently expressed in Escherichia coli , after renaturation dimeric M r 26000 was prepared with purity greater 98%. The recombinant functionally active demonstrated by the induction alkaline phosphatase activity C3H10T1/2 fibroblast cell line (EC 50 70 nM) proteoglycan synthesis embryonic chicken limb...

Phosphorylation of NF-κB p65(RelA) serine 536 is physiologically induced in response to a variety proinflammatory stimuli, but the responsible pathways have not been conclusively unraveled, and function this phosphorylation largely elusive. In contrast previous studies, we found no evidence for role c-Jun N-terminal kinase, p38 extracellular signal-regulated or phosphatidylinositol 3-kinase interleukin-1- tumor necrosis factor-induced Ser-536 phosphorylation, as revealed by pharmacological...

A hallmark of inflammation is the burst-like formation certain proteins, initiated by cellular stress and proinflammatory cytokines like interleukin 1 (IL-1) tumor necrosis factor, stimuli which simultaneously activate different mitogen-activated protein (MAP) kinases NF-κB. Cooperation these signaling pathways to induce IL-8, a prototype chemokine causes leukocyte migration activation, was investigated expressing active inactive forms kinases. Constitutively MAP kinase 7 (MKK7), an...

Streptococcus pneumoniae is the major cause of community-acquired pneumonia and one most common causes death by infectious disease in industrialized countries. Little known concerning mechanisms target cell activation this disease. The present study shows that NF-κB p38 MAPK signaling pathways contribute to chemokine synthesis lung epithelial cells response pneumococci. In infected lungs mice pneumococci stimulate expression interleukin (IL)-8 homolog keratinocyte-derived...

Binding sites for the dimeric transcription factor activator protein (AP)-1 are found in numerous immunoregulatory and inflammatory genes. The precise mechanisms by which AP-1 activates or represses immune response genes particular roles of individual subunits responses largely unknown. We report here that c-Fos Fos-related antigen-1 (Fra-1), two inducible components AP-1, recruited to endogenous interleukin (IL)-8 promoter an IL-1-dependent manner. IL-8 synergizes this effect with p65...

The proinflammatory cytokine interleukin (IL)-1 activates several hundred genes within the same cell. This occurs in part by activation of MKK7-JNK-c-Jun signaling pathway whose precise role regulation individual inflammatory is still incompletely understood. To identify that are under specific control activated JNK, we used a JNK-MKK7 fusion protein. Genome-wide microarray analysis revealed EGR-1 as transcript was most strongly induced JNK-MKK7. IL-1-stimulated mRNA and protein expression...

Interleukin-1 (IL-1)-induced mRNA expression of ccl2 (also called MCP-1), a prototypic highly regulated inflammatory gene, is severely suppressed in cells lacking c-Jun or Jun N-terminal protein kinase 1 (JNK1)/JNK2 genes and only partially restored expressing c-Jun(SS63/73AA) mutant protein. We used chromatin immunoprecipitation to identify three c-Jun-binding sites located the far 5' region close transcriptional start site 3' murine human genes. Mutational analysis revealed that latter two...

ISBN 978-3-89606-193-5 Deutschland ist eine Gesellschaft des langen Lebens. Bereits heute leben in mehr 65-jahrige und altere Menschen als 15-jahrige jungere. Und die Altersstruktur wird sich weiter zugunsten der alteren verschieben. Gesundheit im Alter zukunftig ein Thema von hoher individueller gesellschaftlicher Bedeutung. Mit fortschreitendem deutlicher Anstieg Gesundheitsproblemen zu beobachten. Auch Komplexitat vorliegenden Beeintrachtigungen wachst mit dem Alter. Ein groser Teil...

The transcription factor activator protein (AP)-1 plays crucial roles in proliferation, cell death, and the immune response. c-JUN is an important component of AP-1, but only very few response genes have been identified to date. Activity controlled by NH2-terminal phosphorylation (JNP) its transactivation domain a family JUN-NH2-terminal kinases (JNK). JNK form stable complex with vitro vivo. We targeted this interaction means cell-permeable peptide containing JNK-binding (δ) human c-JUN....

The inflammatory response is characterized by the induction (or repression) of hundreds genes. activity many these genes controlled MAPKs and IκB kinase-NFκB pathway. To reveal effects blocking pathways simultaneously, fibroblasts were infected with retroviruses encoding TAK1K63W, an inactive mutant protein kinase TAK1. Expression this inhibited tumor necrosis factor (TNF)-induced activation NFκB, JNK, p38 MAPK sensitized cells to TNF-induced apoptosis. 23 different microarray experiments...

Yersinia enterocolitica triggers activation of the nuclear factor (NF)-κB and production proinflammatory chemokine interleukin (IL)-8 in intestinal epithelial cells. This is due to adhesion bacteria via their outer membrane protein invasin host Using Clostridium difficile toxins that specifically inactivate small GTPases, transfection inhibitory proteins Rho-GTPases, we demonstrate Rac1, but not Cdc42 or Rho, required for NF-κB by invasin. Invasin activated mitogen kinases (MAPK) p38 c-Jun...

Abstract Objectives We aimed to develop simple and rapid HPLC methods for determination of amoxicillin clindamycin in human plasma. Methods Plasma samples were pretreated by direct deproteinization with acetonitrile the analytical separation took place on a reverse phase Poroshell 120 EC-C18 column (2.7 μm, 2.1 × 100 mm) gradient acetonitrile. UV detection at 229 nm 204 was used antibiotics Results The calibration curves linear over concentration ranges 1–100 mg/L 1–15 correlation...

The prevalence of obesity is increasing, and the origins metabolic dysfunction may be traced back to fetal life. Currently, overweight pregnant women are advised substitute sugar-sweetened beverages with diet drinks containing artificial sweeteners. Recent evidence suggests that consumption sweeteners during pregnancy increases risk in child, but mechanism unknown. We hypothesized transportation across placenta into circulation amniotic fluid. included 19 who were given an oral dose...

Abstract Objective The aim of the study is to provide insight into real‐world use therapeutic drug monitoring ( TDM ) for most common antiseizure medications ASMs ). Methods In total, 137 586 samples from period 2019–2023 were collected five main Danish laboratories performing TDM. A previously described algorithm developed exclude abnormal results patient data was applied. This resulted in inclusion 84 951 53 406 patients. Concentration ranges calculated as 10th 90th percentiles datasets...

Background: Metastatic renal cell carcinoma (mRCC) is notably resistant to chemotherapy and radiotherapy. However, tyrosine kinase inhibitors (TKIs) checkpoint immunotherapy have significantly improved outcomes. Still, about 20% of patients experience disease progression as their best response TKIs, 16–63% endure severe toxicities, reducing quality life. Optimizing dosing therefore essential. Therapeutic drug monitoring (TDM) a promising strategy for individualizing treatment. The TKI-TDM...

Objective Timing of administration antibiotics and concentrations in maternal blood the umbilical cord are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin mothers infants at birth relation time elapsed from delivery minimal inhibitory concentration (MIC) GBS. Main outcome measures Penicillin G dose delivery. Results In 44 mother–infant dyads, median was 0.2...

Artificial sweeteners (ASs) are calorie-free chemical substances used instead of sugar to sweeten foods and drinks. Pregnant women with obesity or diabetes often recommended substitute sugary products ASs prevent an increase in body weight. However, some recent controversy surrounding relates concerns about the risk caused by a variety metabolic changes, both mother offspring. This study addressed these investigated biodistribution plasma breast milk lactating clarify whether can transfer...