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.
Abstract Bilastine, a second-generation antihistamine, is commonly prescribed for managing allergic rhinoconjunctivitis and urticaria due to its prolonged action. However, its therapeutic potential is constrained by poor water solubility and low oral bioavailability. This study aimed to enhance bilastine dissolution and patient compliance by formulating a nanosuspension-based orodispersible film (ODF). An anti-solvent precipitation method was employed to produce nanosuspension using different hydrophilic stabilizers (Soluplus®, Poloxamer 188, and PEG 6000). The influence of formulation parameters, such as the stabilizer ratio, the anti-solvent ratio, stirring speed, and the stabilizer type, on particle size and polydispersity index (PDI)
... Show MoreThe aim of the present study is to formulate floating effervescent microsponge tablet of the narrow absorption window drug, Baclofen (BFN) for controlling drug release and thereby decrease the side effect of the drug. The microsponges of BFN were prepared by non-aqueous emulsion solvent diffusion method (oil in oil emulsion method). The effects of drug: polymer ratio, stirring time and type of Eudragit polymer on the physical characteristics of microsponges were investigated and characterized for production yield, loading efficiency, particle size, surface morphology, and in vitro drug release from microsponges. The selected microsponge formula was incorporated into the floating effervescent gastro-retentive tablet. The prepared fl
... Show MoreThe objective of the investigation was to analyze the structure and administration of the political system in Iraq (post-ISIS). After 2003, the Iraqi political system suffered the fundamental problem of its failure to achieve the political and social inclusion that characterizes democratic systems, to guarantee the establishment of a "state for all", while respecting differences. Political representation has moved from the system of sectarian ethnic components, under the title of consensual democracy, to the representation of leaders and the realization of their interests and the interests of their parties at the expense of the groups that claim to represent them, which complicates the problem. In this sense, the new political syste
... Show MoreThe excessive and rapid urban growth witnessed by most cities in the world can be a cause of diseases and epidemics, especially those problems related to population, which include problems of transportation and increase in density in the centers, in addition to the lack of interest in planning and designing those cities to take into account the health aspect of the city and obtain The health well-being of the population, and each of these problems has negative effects on health in general and on human health in particular through its prevalence. Therefore, many concepts that serve as a tool for achieving public health and the physical health of the population have emerged, including the concept of city health, which is defined as cities
... Show MoreMetal oxide nanoparticles, including iron oxide, are highly considered as one of the most important species of nanomaterials in a varied range of applications due to their optical, magnetic, and electrical properties. Iron oxides are common compounds, extensive in nature, and easily synthesized in the laboratory. In this paper, iron oxide nanoparticles were prepared by co-precipitation of (Fe+2) and (Fe+3) ions, using iron (II and III) sulfate as precursor material and NH4OH solution as solvent at 90°C. After the synthesis of iron oxide particles, it was characterized using X-ray diffraction (XRD), infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These tests confirmed the obtaining o
... Show MoreThis research investigated concentrations of the copper and cadmium in road dust gathered from varied locations in Baghdad, Iraq. Six residential areas (three from Karkh district and three from Rusafa district) were selected as a control sample. Samples were collected from the rooftops using polyethylene bagsand analyzed using an elemental determination device with a Contra 700 atomic spectrometer to determine levels of these heavy metals. The results showed significant elevations in cadmium in Al-Waziria, -0.01 and Al-Baladiyyat, -0.01, respectively (P<0.05) for each of them compared to the blank value. However, there were insignificant differences in cadmium (Cd) contamination in
Background/Objectives: Cancer pain affects 55–95% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent advances in cancer pain pathophysiology and management, focusing on molecular and cellular mechanisms, emerging pharmacological, interventional and technological therapies and key evidence gaps to inform future precision-based pain management strategies. Methods: Following PRISMA-ScR methodology, we searched PubMed, Embase, Scopus, and Web of Science for studies published between January 2022 and Septem
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