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.
Stealthy intracellular bacterial pathogens are known to establish persistent and sometimes lifelong infections. Some of these pathogens also have a tropism for the reproductive system, thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrate that
This research will cover different aspects of estimating process of construction work in a desert area. The inherent difficulties which accompany the cost estimating of the construction works in desert environment in a developing country, will stem from the limited information available, resources scarcity, low level of skilled workers, the prevailing severe weather conditions and many others, which definitely don't provide a fair, reliable and accurate estimation. This study tries to present unit price to estimate the cost in preliminary phase of a project. Estimations are supported by developing mathematical equations based on the historical data of maintenance, new construction of managerial and school projects.
... Show More2,2'-(1-(3,4-bis(carboxydichloromethoxy)-5-oxo-2,5-dihydrofuran-2-yl)ethane-1,2-diyl)bis(oxy)bis(2,2-dichloroacetic acid) a derivative of L-ascorbic acid was prepared by reaction of L-ascorbic acid with trichloroacetic acid (1:4) ratio, in the presence of potassium hydroxide. A series of new metal complexes of this ligand were prepared by a reaction with the chlorides of Cd(II), Co(II), Ni(II), Cu(II) and Zn(II). The new ligand and its complexes were identified by C.H.N., IR, UV-visible spectra, Thermogravimetric analysis (TGA), as well as 1H, 13C-NMR and Mass spectra for ligand L. The complexes were also identified by molar conductance, atomic absorption, magnetic susceptibility and X-ray diffraction for Cu (II) complex. FT-IR spectra
... Show MoreCheckpoint inhibitors are a type of immune therapy used to treat different types of cancers. These drugs block different checkpoint proteins, for example, CTLA-4, PD-1, and PD-L1 inhibitors.
They block proteins that stop the immune system from attacking the cancer cells. Checkpoints are also described as a type of monoclonal antibody that antagonizes binding between B7 to CTLA-4 and PD-L1 to PD-1.
Immune checkpoint inhibitors are used to treat BARCA mutated triple-negative breast cancer (TNBCS) in patients who do not respond to chemotherapy, and also in the treatment of highly mutated and solid tumors such as brain tumors, liver, and pancreatic cancers.
Immune checkpoint inhibitors exhibit an effect on solid tumo
... Show MoreThis study examines the factors that affect oral participation of six Arab postgraduate students (two Iraqis, two Jordanians, and two Libyans), namely, three male participants and three female participants. For this purpose, a semi-structured interview was employed. The results showed that female as well male interviewees share some factors that make oral participation in classroom disheartening. These factors include high levels of anxiety, lack of confidence, shyness, and lack of preparation. It was also that there is no difference between male and female interviewees in relation to the factors that make them feel disheartened from oral classroom participation.
Colorectal cancer (CRC) is the most common gastrointestinal malignancy and one of the top ten common cancers worldwide with approximately 2 million cases. There are multiple risk factors that could lead to CRC emergence; of which are genetic polymorphisms. Excision repair cross-complementing group 2 (ERCC2) gene encodes for ERCC2 enzyme which plays a crucial role in maintaining genomic integrity by removing DNA adducts. Several studies suggested that there could be a link between genetic polymorphisms of ERCC2 gene and the risk of CRC development. Hence the present study aims to validate the relationship between the following ERCC2 single nucleotide polymorphisms (rs13181, rs149943175, rs530662943, and rs1799790) and CRC susceptibility. A t
... Show Moreraqi species of (Euphorbia lathyris F. Euphorbiaceae) have been used in the present study to evaluate genotoxicity of petroleum ether fraction in two doses (100mg/kg and 200mg/kg) on bone marrow cells in mice for seven successive days, comparing their effects with a positive control (methotrexate at a dose 20 mg/kg). Both doses of petroleum ether fraction of Euphorbia Lathyris significantly decrease mitotic index (P<0.05) compared to dimethylsulfoxide (negative control) group. For total chromosomal aberration, the petroleum ether fraction of Euphorbia lathyris (in both doses) produced significant increase (P<0.05) compared to dimethyl sulfoxide (negative control) group .at the same time, 20mg/kg methotrexate significantly increases (P<0.05)
... Show MoreSome coordination complexes of Co(ІІ), Ni(ІІ), Cu(ІІ), Cd(ІІ) and Hg(ІІ) are reacted in ethanol with Schiff base ligand derived from of 2,4,6- trihydroxybenzophenone and 3-aminophenol using microwave irradiation and then reacted with metal salts in ethanol as a solvent in 1:2 ratio (metal: ligand). The ligand [H4L] is characterized by FTIR, UV-Vis, C.H.N, 1H-NMR,13C-NMR, and mass spectra. The metal complexes are characterized by atomic absorption, infrared spectra, electronic spectra, molar conductance, (C.H.N for Ni(ІІ) complex) and magnetic moment measurements. These measurements indicate that the ligand coordinates with metal (ІІ) ion in a tridentate manner through the nitrogen and oxygen atoms of the ligand, octahed
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