A5000314948- Nitric Oxide and Endothelin Effects
- Glutathione Transferases and Polymorphisms
- Sulfur Compounds in Biology
- Eicosanoids and Hypertension Pharmacology
- Redox biology and oxidative stress
- Protein Kinase Regulation and GTPase Signaling
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Oral microbiology and periodontitis research
- Adipose Tissue and Metabolism
- Selenium in Biological Systems
- Cardiovascular Function and Risk Factors
- Cancer, Hypoxia, and Metabolism
- Tuberculosis Research and Epidemiology
- Bacterial biofilms and quorum sensing
- Neuroinflammation and Neurodegeneration Mechanisms
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Atherosclerosis and Cardiovascular Diseases
- Inflammatory mediators and NSAID effects
- Congenital heart defects research
- Receptor Mechanisms and Signaling
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- Antioxidant Activity and Oxidative Stress
Frederick National Laboratory for Cancer Research
2004-2025
MultiMedica
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2025
Leidos (United States)
2013-2024
Leidos Biomedical Research Inc. (United States)
2024
Górnośląskie Centrum Medyczne
2021
Medical University of Silesia
2021
Jagiellonian University
2017
University of Rome Tor Vergata
2016
University of Sassari
2016
ABSTRACT The proteins belonging to the Fur family are global regulators of gene expression involved in response several environmental stresses and maintenance divalent cation homeostasis. Mycobacterium tuberculosis genome encodes two Fur-like proteins, FurA a protein formerly annotated FurB. Since this paper we show that it represents zinc uptake regulator, refer as Zur. encoding Zur is found an operon together with second transcriptional regulator (Rv2358). In previous work demonstrated...
Individual oncogenic KRAS mutants confer distinct differences in biochemical properties and signaling for reasons that are not well understood. activity is closely coupled to protein dynamics regulated through two interconverting conformations: state 1 (inactive, effector binding deficient), 2 (active, enabled). Here we use 31P NMR delineate the populations present wild-type (WT) common (G12C, G12D, G12V, G13D, Q61L) bound its natural substrate GTP or a commonly used nonhydrolyzable analogue...
We report the stabilization of nitric oxide (NO) prodrugs and anticancer lead compounds, PABA/NO (O2-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) "Double JS-K" 1,5-bis-{1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato}-2,4-dinitrobenzene, through their incorporation into polymer-protected nanoparticles. The were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid...
Using an orthotopic model of renal cell carcinoma, we showed previously that IL-2/anti-CD40 immunotherapy resulted in synergistic anti-tumor responses, whereas IL-2 or α-CD40 alone mediated partial transient effects. We now show treatment tumor-bearing mice with IL-2/α-CD40, but not α-CD40, induced significant nitric oxide synthase (NOS) 2 expression tumor-associated macrophages. In control-treated (low NO), NOS2 inhibition reduced tumor burden. However, during (high macrophage depletion...
Rationale: Long living individuals show delay of aging, which is characterized by the progressive loss cardiovascular homeostasis, along with reduced endothelial nitric oxide synthase activity, dysfunction, and impairment tissue repair after ischemic injury. Objective: Exploit genetic analysis long to reveal master molecular regulators physiological aging new targets for treatment disease. Methods Results: We that polymorphic variant rs2070325 (Ile229Val) in...
Specific promoter recognition by bacterial RNA polymerase is mediated σ subunits, which assemble with core enzyme (E) during transcription initiation. However, 70 (the housekeeping subunit) and S (an alternative subunit mostly active slow growth) recognize almost identical sequences, thus raising the question of how selectivity achieved in cell. To identify novel sequence determinants for selective recognition, we performed run-off/microarray (ROMA) experiments saturated either (Eσ ) or...
Abstract Aims Here, we aimed to determine the therapeutic effect of longevity-associated variant (LAV)-BPIFB4 gene therapy on atherosclerosis. Methods and results ApoE knockout mice (ApoE−/−) fed a high-fat diet were randomly allocated receive LAV-BPIFB4, wild-type (WT)-BPIFB4, or empty vector via adeno-associated viral injection. The primary endpoints study assess (i) vascular reactivity (ii) atherosclerotic disease severity, by Echo-Doppler imaging, histology ultrastructural analysis....
Abstract Aims The ageing heart naturally incurs a progressive decline in function and perfusion that available treatments cannot halt. However, some exceptional individuals maintain good health until the very late stage of their life due to favourable gene–environment interaction. We have previously shown carriers longevity-associated variant (LAV) BPIFB4 gene enjoy prolonged spans lesser cardiovascular complications. Moreover, supplementation LAV-BPIFB4 via an adeno-associated viral vector...
Abstract The glycine to cysteine mutation on codon 12 of KRAS (KRASG12C) is found in ~15% non-small cell lung cancers and a low percentage colorectal pancreatic adenocarcinomas. This activating pushes the balance cellular towards its active, GTP-bound (ON) state that signals downstream drives proliferation. Recently approved inhibitors KRASG12C bind sequester oncogenic protein inactive GDP-bound (OFF) state, have demonstrated clinical efficacy; however, median duration response has been...
Journal Article Co-transcriptional production of RNA–DNA hybrids for simultaneous release multiple split functionalities Get access Kirill A. Afonin, Afonin 1Center Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA, 2Basic Science Leidos Biomedical Research, Inc., Frederick National Laboratory 3Gene Regulation and Chromosome Biology Laboratory, Center NCI, 4HIV Drug Resistance USA 5Chemical Search other works by this author on: Oxford Academic PubMed Google Scholar...
Whole-blood and plasma selenium (Se) concentrations, red blood cell glutathione peroxidase activities, concentrations were investigated in 49 healthy pregnant women. Mean whole-blood Se started to decline after the 16th week 26th of pregnancy. The lowest values noted just before delivery. Negative correlations found between gestational age both concentrations: (r = ––0.560 (p < 0.001) r ––0.553 0.001), respectively. Plasma activities decrease 20th 30th pregnancy, respectively, delivery...
Non–small-cell lung cancer is among the most common and deadly forms of human malignancies. Early detection unusual, there are no curative therapies in cases. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs a growing class promising NO-based therapeutics. Here, we show that <i>O</i><sup>2</sup>-(2,4-dinitrophenyl)-1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) potent cytotoxic agent against subset non–small-cell cell lines both vitro as xenografts mice. JS-K...
People that reach extreme ages (Long-Living Individuals, LLIs) are object of intense investigation for increase/decrease genetic variant frequencies, methylation levels, protein abundance in serum and tissues. The aim these studies is the discovery mechanisms behind LLIs longevity identification markers well-being. We have recently associated a BPIFB4 haplotype (LAV) with exceptional under homozygous model, identified CD34+ subjects express higher transcript as compared to control...
JS-K is a nitric oxide (NO)-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in variety cancer models both vitro vivo. The current study metabolic actions was undertaken to investigate mechanisms its cytotoxicity. Consistent with model chemical reactions, activating step metabolism cell dearylation by glutathione (GSH) via nucleophilic aromatic substitution reaction. resulting product (CEP/NO anion)...
Abstract Aims Homozygosity for a four‐missense single‐nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long‐living individuals. Delivery this longevity‐associated variant (LAV) improved revascularisation and reduced endothelial dysfunction atherosclerosis mice through mechanism involving stromal cell‐derived factor‐1 (SDF‐1). Here, we investigated if delivery LAV‐BPIFB4 may attenuate progression diabetic cardiomyopathy. Methods results Compared with age‐matched lean...
Abstract KRAS is the most commonly mutated oncogene, altered in approximately 15% of human cancers. While inhibitors KRASG12C have shown promising clinical efficacy, there are currently no approved targeted therapies against other variants, resulting a significant underserved patient population across several major cancer types, including pancreatic carcinoma (PDAC), colorectal (CRC), and non-small cell lung (NSCLC). To address this unmet need, we developed BBO-11818: potent, selective,...
K- ras is frequently mutated in lung adenocarcinomas. Recent discovery that wild-type tumor suppressive the raises a question: how mutant aggressively oncogenic? We hypothesized K-ras might lead to generation of reactive oxygen species (ROS) and DNA damage, contributing malignant transformation. stably transfected human rasV12 into non-transformed peripheral mouse epithelial cells (E10 line). Constitutively active E10 led highly significant ( P < 0.001) increased level peroxides,...
In Gram-negative bacteria, production of adhesion factors and extracellular polysaccharides (EPS) is promoted by the activity diguanylate cyclases (DGCs), a class enzymes able to catalyse synthesis signal molecule bis-(3′,5′)-cyclic di-guanylic acid (c-di-GMP). this report we show that in Escherichia coli , overexpression YddV protein, but not other DGCs such as AdrA YcdT, induces EPS poly- N -acetylglucosamine (PNAG) stimulating expression pgaABCD PNAG-biosynthetic operon. Stimulation PNAG...