The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, is a potent ligand for aryl hydrocarbon receptor (AhR). In the current study, we made an exciting observation that naive C57BL/6 mice that were exposed i.p. to TCDD showed massive mobilization of myeloid-derived suppressor cells (MDSCs) in the peritoneal cavity. These MDSCs were highly immunosuppressive and attenuated Con A–induced hepatitis upon adoptive transfer. TCDD administration in naive mice also led to induction of several chemokines and cytokines in the peritoneal cavity and serum (CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL2, CXCL5, CXCL9, G-CSF, GM-CSF, VEGF, and M-CSF) and chemokine receptors on MDSCs (CCR1, CCR5, and CXCR2). Treatment with CXCR2 or AhR antagonist in mice led to marked reduction in TCDD-induced MDSCs. TCDD-induced MDSCs had high mitochondrial respiration and glycolytic rate and exhibited differential microRNA (miRNA) expression profile. Specifically, there was significant downregulation of miR-150-5p and miR-543-3p. These two miRNAs targeted and enhanced anti-inflammatory and MDSC-regulatory genes, including IL-10, PIM1, ARG2, STAT3, CCL11 and its receptors CCR3 and CCR5 as well as CXCR2. The role of miRs in MDSC activation was confirmed by transfection studies. Together, the current study demonstrates that activation of AhR in naive mice triggers robust mobilization of MDSCs through induction of chemokines and their receptors and MDSC activation through regulation of miRNA expression. AhR ligands include diverse compounds from environmental toxicants, such as TCDD, that are carcinogenic to dietary indoles that are anti-inflammatory. Our studies provide new insights on how such ligands may regulate health and disease through induction of MDSCs.
The formation of a Schiff-base with N2O2 donor atoms derived from the hydrazine segment and its metal complexes are reported. The Schiff-base ligand; N’-((1R,2S,4R,5S,Z)-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-ylidene)furan-2-carbohydrazide (HL) was prepared from the reaction of furan-2-carbohydrazide with (1R, 2R, 4R, 5S)-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-one (M1) in ethanol medium. The reaction of the title ligand with selected metal ions Cr(III), Mn(II), Ni(II), Cu(II), Zn(II) and Cd(II) gave complexes with the general formula [M(L)Cl2], (where: M = Cr(III), Mn(II), Ni(II), Cu(II), Zn(II) and Cd(II)). Spectroscopic analyses Fourier transform infrared (FT-IR), Nuclear Magnetic Resonance (NMR) Carbon-13 nuclear magnetic res
... Show MoreAxial spondyloarthritis (axSpA) is a chronic rheumatic inflammatory disease affecting mainly the spine and sacroiliac joints. Since the copper-to-zinc ratio (Cu/Zn) indicates an inflammatory response, the change in ratio is expected to correlate with axSpA. This study compared levels of Cu/Zn in the serum of axSpA patients. Serum samples were obtained from 53 patients with axSpA divided according to biological treatment into cohorts A and B, and 28 healthy control as cohort C. Serum levels of Cu and Zn were determined first by a fully automated chemistry analyzer TC-Matrix Plus, then the ratio was obtained. The elevated serum Cu concentration means of cohort B (189.32 ± 13.808 µg/dL) compared to cohort A (168.85 ± 7.244 µg/dL) a
... Show MoreIn this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)- thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by th
... Show MoreBackground: Peripheral giant cell lesion (PGCL) and central giant cell lesion (CGCL) of the jaws have a distinct clinical behavior.Giant cell tumour (GCT) is a benign locally aggressive neoplasm affects the long bones. Both lesions are characterized histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. The WW domain-containing oxidoreductase (WWOX) gene is located at 16q23.1–16q23.2, a region that spans the second most common human fragile site, FRA16D, at 16q23.2.The Ki-67 antigen is a nuclear protein that is associated with and may be necessary for cellular proliferation.Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent fr
... Show MoreIn this study, the antimicrobial properties of newly synthesized Schiff bases (4a-4e) and thiazolidinone compounds (5a-5e) generated from 3,5-dinitrobenzoic acid were assessed. These compounds were obtained by reacting 3,5-dinitrobenzoic acid (1) with ethanol in a few drops of concentrated H2SO4 to produce the ester (2). The acid hydrazide (3), which was produced by treating the ester with hydrazine hydrate, reacted with the proper aldehydes, including 4-bromobenzaldehyde, 4-chlorobenzaldehyde, 4-hydroxybenzaldehyde, 4-methoxybenzaldehyde, and 4-hydroxy-3-methoxybenzaldehyde, respectively, to form Schiff bases (4a-4e). The thiazolidinone compounds (5a-5e) were produced by the cyclocondensation reaction of compounds (4a-4e) with thio
... Show MoreIn this study, the antimicrobial properties of newly synthesized Schiff bases (4a-4e) and thiazolidinone compounds (5a-5e) generated from 3,5-dinitrobenzoic acid were assessed. These compounds were obtained by reacting 3,5-dinitrobenzoic acid (1) with ethanol in a few drops of concentrated H2SO4 to produce the ester (2). The acid hydrazide (3), which was produced by treating the ester with hydrazine hydrate, reacted with the proper aldehydes, including 4-bromobenzaldehyde, 4-chlorobenzaldehyde, 4-hydroxybenzaldehyde, 4-methoxybenzaldehyde, and 4-hydroxy-3-methoxybenzaldehyde, respectively, to form Schiff bases (4a-4e). The thiazolidinone compounds (5a-5e) were produced by the cyclocondensation reaction of compounds (4a-4e) with thio
... Show MoreLeishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and
... Show MoreLeishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and
... Show More15 local isolates of Pseudomonas were obtained from 35 samples from several sources such as soil, water and some high-fat foods. The ability of isolates to produce lipase was measured by the size of the clarification zone formed around the colonies on the lipase production medium and by measuring the enzymatic activity and specific enzymatic activity, the isolate M3 was found to be the most efficient for production of the enzyme, This isolate was identified by microscopic, morphological, some biochemical tests and genetic diagnosis of 16S gene sequences by using the (PCR) technique, and then comparing the results obtained with the National Center for Biotechnology Inform
... Show MoreBackground: Anemia of chronic disease (ACD) occurs in the presence of chronic infection, inflammatory conditions or neoplastic conditions despite of adequate iron and vitamins storage. Gingivitis is the inflammation of the gingiva, periodontitis is the inflammation in the periodontium that extend deeper with loss of connective tissue attachment and supporting bone. The main pathogenesis of periodontal diseases and ACD is immune activation. Aims of study: Determine and compare the clinical periodontal parameters (plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL)). Evaluate the hematocrit (Hct) level, red blood cells (RBCs) count and white blood cells (WBCs) c
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