Despite extensive investigations, an effective treatment for sepsis remains elusive and a better understanding of the inflammatory response to infection is required to identify potential new targets for therapy. In this study we have used RNAi technology to show, for the first time, that the inducible lysophosphatidylcholine acyltransferase 2 (LPCAT2) plays a key role in macrophage inflammatory gene expression in response to stimulation with bacterial ligands. Using siRNA- or shRNA-mediated knockdown, we demonstrate that, in contrast to the constitutive LPCAT1, LPCAT2 is required for macrophage cytokine gene expression and release in response to TLR4 and TLR2 ligand stimulation but not for TLR-independent stimuli. In addition, cells transfected to overexpress LPCAT2 exhibited increased expression of inflammatory genes in response to LPS and other bacterial ligands. Furthermore, we have used immunoprecipitation and Western blotting to show that in response to LPS, LPCAT2, but not LPCAT1, rapidly associates with TLR4 and translocates to membrane lipid raft domains. Our data thus suggest a novel mechanism for the regulation of inflammatory gene expression in response to bacterial stimuli and highlight LPCAT2 as a potential therapeutic target for development of anti-inflammatory and anti-sepsis therapies.
Background: CYP1A1 gene polymorphisms and tobacco smoking are among several risk factors for various types of cancers, but their influence on breast cancer remains controversial. We analyzed the possible association of CYP1A1 gene polymorphisms and tobacco smoking-related breast cancer in women from Iraq. Materials and methods: In this case-control study, gene polymorphism of CYP1A1 gene (CYP1A1m1, T6235C and CYP1A1m2, A4889G) of 199 histologically verified breast cancer patients' and 160 cancer-free control women's specimens were performed by using PCR-based restriction fragment length polymorphism. Results: Three genotype frequencies (TT, TC, and CC) of CYP1A1m1T/C appeared in 16.1, 29.6, and 54.3% of women with breast cancer, respectiv
... Show MoreFreedom of opinion and expression occupy the first place among the concerns of countries and international organizations. And it is also the basis of contemporary freedom because it is the foundation for achieving freedom in other fields such as politics, economics, education, etc.. The constitutions of the state have ensured that almost the entire freedom to express an opinion in all its forms either orally or writing or images of expressions, but these freedoms are identified within the law. Most countries announced their commitment to the international conventions and texts issued by international and regional organization like the Universal Declaration of Human Rights in 1948, and the International Covenant on Civil and Political Rig
... Show MoreThis paper presents a study (experimentally) for strengthening reinforced concrete (RC) beams with Near-Surface-Mounted (NSM) technique. The use of this technique with CFRP strips or rebars is an efficient technology for increasing the strength for flexure and shear or for repairing damaged reinforced concrete (RC) members. The objective of this research is to study, experimentally, RC beams either repaired or strengthened with NSM CFRP strips and follow their flexural behavior and failure modes. NSM-CFRP strips were used to strengthen three RC beam specimens, one of them was initially strengthened and tested up to failure. Four beam specimens have been initially subjected to preloading to 50% and 80% of ultimate load. Two of the sp
... Show MoreRheumatoid arthritis (RA) is characterized by persistent joint inflammation, which is a defining feature of this chronic inflammatory condition. Considerable advancements have been made in the field of disease-modifying anti-rheumatic medicines (DMARDs), which effectively mitigate inflammation and forestall further joint deterioration. Anti-tumor necrosis factor-alpha (TNF-α) drugs, which are a class of biological DMARDs (bDMARDs), have been efficaciously employed in the treatment of RA in recent times Adalimumab, a TNF inhibitor, has demonstrated significant efficacy in reducing disease symptoms and halting disease progression in patients with RA. However, its use is associated with major side effects and high costs. In addition,
... Show MoreGhrelin and leptin are hunger hormones related to type 2 diabetes mellitus (T2DM), and the pathogenesis of T2DM is the abnormality in insulin secretion and insulin resistance (IR). The aim of this study is to evaluate ghrelin and leptin concentrations in blood and to specify the relationship of these hormones as dependent variables with some biochemical and clinical measurements in T2DM patients. In this study, forty one T2DM and forty three non-diabetes mellitus (non-DM) subjects, aged between 40-60 years and with normal weight, were enrolled. Fasting serum ghrelin and leptin were estimated by enzyme-linked immunosorbent assay (ELISA). In our results ghrelin was significantly increased, and leptin was significantly decreased, in T2DM pa
... Show MoreThe angiotensin converting enzyme (ACE) I\D gene polymorphism influences the blood ACE enzyme activity. Renoprotective effect of ACE inhibitors (ACEIs) varies among patients due to genetic variation, particularly in Renin-Angiotensin-Aldosterone System genes. This study investigates the genetic variations of ACE I\D and AGT1RA1166C gene polymorphisms in the antiproteinuric effect of ACEI therapy in type 2 diabetes mellitus (T2DM) patients. This is a cross-sectional study that included 76 T2DM patients who are ACEI users, divided into two groups: T2DM without diabetic kidney disease (DKD) included 31 patients, and T2DM with DKD included 45 patients. Urine samples were taken for measurement of urine albumin and creatinine, then calcul
... Show MoreTo evaluate the Interaction of Mn(II), Fe(II), Co(II), Ni(II),Cu(II), Zn(II) And Cd(II) Mixed- Ligand Complexes of cephalexin mono hydrate (antibiotics) And Furan-2-Carboxylic Acid To The Different DNA Sources. All the metal complexes were observed to cleave the DNA. A difference in the bands of complexes .The cleavage efficiency of the complexes compared with that of the control is due to their efficient DNA-binding ability and the other factors like solubility and bond length between the metal and ligand may also increase the DNA-binding ability. The ligands (Cephalexin mono hydrate (antibiotics) and Furan-2- Carboxylic acid and there newly synthesized metal complexes shows good antimicrobial activities and Binding DNA , thus, can be used
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