TNF-α induces a pro-inflammatory phenotypic shift in monocytes through ACSL1 : Relevance to metabolic inflammation

Background/Aims: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes. Methods: Monocytes (Human monocytic THP-1 cells) were stimulated with TNF-α. Inflammatory phenotypic markers (CD16, CD11b, CD11c and HLA-DR) expression was determined with real time RT-PCR and flow cytometry. IL-1β and MCP-1 were determined by ELISA. Signaling pathways were identified by using ACSL1 inhibitor, ACSL1 siRNA and NF-κB reporter monocytic cells. Phosphorylation of NF-κB was analyzed by western blotting and flow cytometry. Results: Our data show that TNF-α induced significant increase in the expression of CD16, CD11b, CD11c and HLA-DR. Inhibition of ACSL1 activity in the cells with triacsin C significantly suppressed the expression of these inflammatory markers. Using ACSL-1 siRNA, we further demonstrate that TNF-α-induced inflammatory markers expression in monocytic cells requires ACSL1. In addition, IL-1b and MCP-1 production by TNF-α activated monocytic cells was significantly blocked by the inhibition of ACSL-1 activity. Interestingly, elevated NF-κB activity resulting from TNF-α stimulation was attenuated in ACSL1 deficient cells. Conclusion: Our findings provide an evidence that TNF-α-associated inflammatory polarization in monocytes is an ACSL1 dependent process, which indicates its central role in TNF-α-driven metabolic inflammation. © 2019 The Author(s).Peer reviewe

Correlation Profile of Suppression of Tumorigenicity 2 and/or Interleukin-33 with Biomarkers in the Adipose Tissue of Individuals with Different Metabolic States

Purpose: The suppression of tumorigenicity 2 (ST2) has two main splice variants including a membrane bound (ST2) form, which activates the myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-kappa B) signaling pathway, and a secreted soluble form (sST2), which acts as a decoy receptor for ST2 ligand, interleukin (IL)-33. The IL-33/ST2 axis is protective against obesity, insulin resistance, and type 2 diabetes (T2D). In humans, adipose tissue IL-33 displays distinct correlation profiles with glycated hemoglobin, ST2, and other immunometabolic mediators, depending on the glycemic health of the individuals. We determined whether adipose tissue ST2 displays distinct correlation profiles with immunometabolic mediators and whether ST2 and/or IL-33 are correlated with intracellular signaling molecules. Patients and Methods: A total of 91 adults with normal glycemia, prediabetes, and T2D were included. After measuring their anthropometric and biochemical parameters, subcutaneous adipose tissues were isolated and mRNA expression of biomarkers was measured. Results: In individuals with normal glycemia, adipose tissue ST2 was directly correlated with chemokine (C-C motif) ligand (CCL)-2, CCL5, IL-12, fibrinogen-like protein 2 (FGL2) and interferon regulatory factor (IRF)-4, but inversely correlated with cytochrome C oxidase subunit 7A1. IL-33 and ST2 were directly correlated with tumor necrosis factor receptorassociated factor 6 (TRAF6), NF-kappa B, and nuclear factor of activated T-cells 5 (NFAT5). In individuals with prediabetes, ST2 was inversely correlated with IL-5, whereas IL-33 but not ST2 was directly correlated with MyD88 and NF-kappa B. In individuals with T2D, ST2 was directly correlated with CCL2, IL-1 beta, and IRF5. IL-33 and ST2 were directly correlated with MyD88, TRAF6, and NF-kappa B. Conclusion: Adipose tissue ST2 and IL-33 show different correlation profiles with various immunometabolic biomarkers depending on the metabolic state of the individuals. Therefore, targeting the IL-33/ST2 axis might form the basis for novel therapies to combat metabolic disorders.Peer reviewe

Asphericity of a length four relative presentation

We consider the relative group presentation P = where X = { x \} and R = { xg_1 xg_2 xg_3 x^{-1} g_4 }. We show modulo a small number of exceptional cases exactly when P is aspherical. If the subgroup H of G is given by H = then the exceptional cases occur when H is isomorphic to one of C_5,C_6,C_8 or C_2 X C_4

Modification of Montmorillonite by new surfactants.

The sodium Montmorillonite is not susceptible to polymer due to its organophobic character and has low basal spacing. This study reports on the effect of three new organic cations including Triethyl Amine (TEA), Tripropyl Amine (TPA) and Trioctyl Amine (TOA) on the basal spacing of the clay as indictors to the sociability of the clay to the incorporation of polymers. The Fourier Transform Infrared spectroscopy (FTIR) was used to evaluate the incorporation of the three organic cations in the clay. The X-ray diffraction technique was utilized to indicate the basal spacing of the treated clay as a measure of the susceptibility of new organoclays. The FTIR, XRD and CHNS elemental analysis results shown that the three new organic cations acrylonitrile/montmorillonite were successfully incorporated in the Montmorollite clay. X-ray diffraction indicates that the basal spacings in acrylonitrile/montmorillonite of the treated clay with TEA, TPA and TOA individually increased by 14.2, 15.1 and 19.5Å, respectively. FTIR spectra illustrate that amine compounds were successfully intercalated into the clay layers

Assessing the effectiveness of a pharmacist-delivered smoking cessation program in the State of Qatar: study protocol for a randomized controlled trial

Background: It had been reported that up to 37% of the adult male population smokes cigarettes in Qatar. The Global Youth Tobacco Survey also stated that 13.4% of male school students aged 13 to 15 years in Qatar smoke cigarettes. Smoking cessation is key to reducing smoking-related diseases and deaths. Healthcare providers are in an ideal position to encourage smoking cessation. Pharmacists are the most accessible healthcare providers and are uniquely situated to initiate behavior change among patients. Many studies have shown that pharmacists can be successful in helping patients quit smoking. Studies demonstrating the effectiveness of pharmacist-delivered smoking cessation programs are lacking in Qatar. This proposal aims to test the effect of a structured smoking cessation program delivered by trained ambulatory pharmacists in Qatar. Methods/Design: A prospective, randomized, controlled trial is conducted at eight ambulatory pharmacies in Qatar. Participants are randomly assigned to receive an at least four-session face-to-face structured patient-specific smoking cessation program conducted by the pharmacist or 5 to 10 min of unstructured brief smoking cessation advice (emulating current practice) given by the pharmacist. Both groups are offered nicotine replacement therapy if feasible. The primary outcome of smoking cessation will be confirmed by an exhaled carbon monoxide test at 12 months. Secondary outcomes constitute quality-of-life adjustment as well as cost analysis of program resources consumed, including per case and patient outcome. Discussion: If proven to be effective, this smoking cessation program will be considered as a model that Qatar and the region can apply to decrease the smoking burden. Trial registration: Clinical Trials NCT02123329.Qatar National Research Fund under its National Priorities Research Program (NPRP)

Chemical synthesis and characterization of N-hydroxy-N-methyl fattyamide from palm oil.

In this study, N-hydroxy-N-methyl fattyamide (HMFA) has been synthesized by refluxing of palm oil and N, methyl hydroxylamine. The products were characterized using the complex formation test of hydroxamic acid group with copper(Π), various technique methods including nuclear magnetic resonance ('H NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and elemental analysis. Parameters that may affect the conversion of palm oil to HMFA including the effect of reaction time, effect of organic solvent and effect of, M, methyl hydroxylamine /oil molar ratio were also investigated in this study. Results of characterization indicate that HMFA was successfully produced from palm oil. The conversion percentage of palm oil into N-hydroxy-N-methyl Fattyamide was around 79. Results also showed that hexane is the best organic solvent to produce the HMFA. The optimum reaction time to achieve the maximum conversion percentage of the palm oil into HMFA was found to be 16 hours, and the optimum molar ration of M, methyl hydroxylamine/oil was found to be 6.5:1.0

Effect of epoxidized palm oil on the mechanical and morphological properties of a PLA–PCL blend

In this study, the effects of epoxidized palm oil (EPO) on the mechanical and morphological properties of a blend of two types of biodegradable polymer, poly(lactic acid) (PLA) and polycaprolactone (PCL), were investigated. The solution-casting process, with chloroform as a solvent, was used to prepare samples. Addition of EPO reduced the tensile strength and modulus but increased elongation at break for the PLA–PCL blend. The highest elongation at break was observed for the blend with 10 % (w/w) EPO content. Scanning electron microscopy (SEM) indicated that the fractured surface morphology of the PLA–PCL blend became more stretched and homogeneous in PLA–PCL–EPO. Possible interactions between the PLA–PCL blend and EPO were also characterized by use of Fourier-transform infrared (FTIR) spectroscopy. Thermal stability was studied by differential scanning calorimetry and thermogravimetric analysis. The results from FTIR and SEM revealed that the miscibility of the PLA–PCL blend was improved by addition of EPO

Synthesis and characterization of fatty hydroxamic acids from triacylglycerides

In this study, fatty haydroxamic acids (FHAs), which have biological activities as antibiotics and antifungal, have been synthesized via refluxing of triacylglycrides, palm olein, palm stearin or corn oil with hydroxylamine hydrochloride. The products were characterized using the complex formation test of hydroxamic acid group with zinc(I), copper(II) and iron(III), various technique methods including nuclear magnetic resonance ((1)H NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and elemental analysis. Parameters that may affect the conversion of oils to FHAs including the effect of reaction time, effect of organic solvent and effect of hydro/oil molar issue were also investigated in this study. Results of characterization indicate that FHAs were successfully produced from triacylglycrides. The conversion percentages of palm stearin, palm olein and corn oil into their fatty hydroxamic acids are 82, 81 and 78, respectively. Results also showed that hexane is the best organic solvent to produce the FHAs from the three oils used in this study. The optimum reaction time to achieve the maximum conversion percentage of the oils to FHAs was found to be 10 hours for all the three oils, while the optimum molar ration of hydro/to oil was found to be 7:1 for all the different three oils

Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity

Steroid receptor RNA activator gene (SRA1) emerges as a player in pathophysiological responses of adipose tissue (AT) in metabolic disorders such as obesity and type 2 diabetes (T2D). We previously showed association of the AT SRA1 expression with inflammatory cytokines/chemokines involved in metabolic derangement. However, the relationship between altered adipose expression of SRA1 and the innate immune Toll-like receptors (TLRs) as players in nutrient sensing and metabolic inflammation as well as their downstream signaling partners, including interferon regulatory factors (IRFs), remains elusive. Herein, we investigated the association of AT SRA1 expression with TLRs, IRFs, and other TLR-downstream signaling mediators in a cohort of 108 individuals, classified based on their body mass index (BMI) as persons with normal-weight (N = 12), overweight (N = 32), and obesity (N = 64), including 55 with and 53 without T2D. The gene expression of SRA1, TLRs-2,3,4,7,8,9,10 and their downstream signaling mediators including IRFs-3,4,5, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1), and nuclear factor-κB (NF-κB) were determined using qRT-PCR and SRA1 protein expression was determined by immunohistochemistry. AT SRA1 transcripts’ expression was significantly correlated with TLRs-3,4,7, MyD88, NF-κB, and IRF5 expression in individuals with T2D, while it associated with TLR9 and TRAF6 expression in all individuals, with/without T2D. SRA1 expression associated with TLR2, IRAK1, and IRF3 expression only in individuals with obesity, regardless of diabetes status. Furthermore, TLR3/TLR7/IRAK1 and TLR3/TLR9 were identified as independent predictors of AT SRA1 expression in individuals with obesity and T2D, respectively. Overall, our data demonstrate a direct association between the AT SRA1 expression and the TLRs together with their downstream signaling partners and IRFs in individuals with obesity and/or T2D