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 antidiabetic thiozolidinediones (TZDs) a class of peroxisome proliferators-activated receptor (PPAR) ligands has recently been the focus of much interest for their possible role in regulation of inflammatory response. The present study was designed to evaluate the anti-inflammatory activity of pioglitazone in experimental models of inflammation in rats. The present study was conducted to evaluate the anti inflammatory effect of TZDs (pioglitazone 3mg/Kg) on acute, sub acute and chronic model of inflammation by using egg-albumin and formalin–induced paw edema in 72 rats, relative to reference drugs Dexamethasone 5mg/Kg and Piroxicam 5mg/Kg. In each inflammation model, 24 rats wer
... Show MoreAmoxicillin 1 was treated with thiosemicarbazide and Phosphoryl chloride to obtain a new derivatives that contains 1,3,4-thiadiazole moiety 2. Schiff bases compounds were synthesized by the reaction of compound 2 with different aldehydes such as benzaldehyde and some substituted Benzaldehyde; p-hydroy, p-Chloro, p-Nitro, p-Dimethylamino, p-Methyl, p-Methoxy, p-Ethoxy to give compounds 3a-h. The obtained compounds have tested towards gram -ve and gram +ve bacteria. The compound shows good to moderate result towards the bacteria.
This study describes the preparation of a new bidentate Schiff base derived from the condensation of Isatin-3-hydrazone with 2-acetylthiophene and the preparation of new series of complexes with a good yield. The prepared ligand was characterized by IR, UV-Vis, C.H.N.S elemental analysis, 1H and 13C NMR, LC-Mass spectroscopy, and physical measurements. Its complexes were analyzed by C.H.N.S elemental analyses, UV-Vis., FTIR, NMR, LC-Mass Spectra, atomic absorption spectroscopy, magnetic susceptibility, and conductivity measurements The results from spectroscopy and measurement studies showed that the ligand coordinated to the metal ion as a bidentate ligand via oxygen and nitrogen, forming an octahedral geometry around it. In vitro antimicr
... Show MoreA series of 4-(methylsulfonyl)aniline derivatives were synthesized in order to obtain new compounds as a potential anti-inflammatory agents with expected selectivity against COX-2 enzyme. In vivo acute anti-inflammatory activity of the final compounds 11–14 was evaluated in rat using an egg-white induced edema model of inflammation in a dose equivalent to 3 mg/Kg of diclofenac sodium. All tested compounds produced significant reduction of paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, the activity of compounds 11 and 14 was significantly higher than that of diclofenac sodium (at 3 mg/Kg) in the 120–300 minute time interval, while compound 12 expressed a comparable effect to that of di
... Show MoreDuring treatment of inflammatory diseases, many conventional therapies (non-steroidal anti-inflammatory drugs) used to relief pain and inflammation. Chronic use of the intended drugs is frequently associated with serious side effect, which may lead to discontinuation of treatment . The efficacy and dose- response effect of ammi majus extraxt (2 , 4, 8 , 16, and 32 mg/rat) were assessed using formalin to induce paw edema in rats as a model of chronic inflammation respectively. In this study, 42 rats were used and allocated into 7 groups each containing 6 rats, representing control (Distilled water) , standard (piroxicam ) and test extract ( 2 , 4 , 8 , 16 and 32 mg/rat of Ammi majus alcoholic e
... Show MorePeriodontitis is one of the most prevalent bacterial diseases affecting man with up to 90% of the global population affected. Its severe form can lead to the tooth loss in 10-15% of the population worldwide. The disease is caused by a dysbiosis of the local microbiota and one organism that contributes to this alteration in the bacterial population is Prophyromonas gingivalis. This organism possesses a range of virulence factors that appear to contribute to its growth and survival at a periodontal site amongst which is its ability to invade oral epithelial cells. Such an invasion strategy provides a means of evasion of host defence mechanisms, persistence at a site and the opportunity for dissemination to other sites in the mouth. However, p
... Show MoreThe prostaglandins inside inflamed tissues are produced by cyclooxygenase-2 (COX-2), making it an important target for improving anti-inflammatory medications over a long period. Adverse effects have been related to the traditional usage of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation, mainly centered around gastrointestinal (GI) complications. The current research involves the creation of a virtual library of innovative molecules showing similar drug properties via a structure-based drug design. A library that includes five novel derivatives of Diclofenac was designed. Subsequently, molecular docking through the Glide module and determining the binding free energy implementing the P
... Show Moreتم تحضير ثلاث معقدات جديدة Ni (II)و Cu (II) و Zn (II) باستخدام الليكند المحضر الجديد من تفاعل حامض مالونيك ثنائي هيدرازايد مع 2-بيريدين كربوكسالديهايد. حيث شخصت المعقدات لمحضرة وكذلك الليكند باستخدام تقنيات مختلفة مثل FT-IR و UV-Vis و Mass و 1H-NMR و 13C-NMR وتحليل العناصر CHN و تقدير محتوى الكلور والموصلية المولارية والحساسية المغناطيسية والامتصاص الذري لتشخيص هذه المركبات. لكل معقد محضر جديد من النيكل والنحاس والزنك ، كشفت نتائج ا
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