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Small-Molecule Ferroptotic Agents with Potential to Selectively Target Cancer Stem Cells
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Abstract<p>Effective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species to induce ferroptosis. Interestingly, we find that drug sensitivity is highest in tumor cells with a mesenchymal phenotype. Furthermore, these compounds showed enhanced toxicity towards mesenchymal breast cancer populations with cancer stem cell properties <italic>in vitro</italic>. In summary, we have identified a new class of small molecule ferroptotic agents that warrant further investigation.</p>
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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Preliminary Pharmacological Evaluation of New Analogues of Diclofenac as Potential Anti-inflammatory Agents
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         A group of amine derivatives [4-aminobenzenesulfonamide derivatives, 2-aminopyridine and 2-aminothiazole] incorporated to α-carbon of diclofenac a well known non-steroidal anti-inflammatory drug (NSAID) to increase bulkiness were designed and synthesized for evaluation as  a potential anti-inflammatory agents with expected COX-2 selectivity. In vivo acute anti-inflammatory activity of the selected final compounds (9, 12 and 13) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (3 mg/Kg) of diclofenac sodium. All tested compounds  produced a significant reduction  in paw edema with respect to the effect of propylene glycol 50

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Publication Date
Tue Oct 01 2019
Journal Name
The Journal Of Immunology
AhR Activation Leads to Massive Mobilization of Myeloid-Derived Suppressor Cells with Immunosuppressive Activity through Regulation of CXCR2 and MicroRNA miR-150-5p and miR-543-3p That Target Anti-Inflammatory Genes
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Abstract<p>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</p> ... Show More
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Publication Date
Fri Jan 03 2020
Journal Name
Annals Of Tropical Medicine And Public Health
Genomic Fingerprinting of Interleukin IL-12RB2 of Nasal Mucosal Stem Cells in Nasal Polyposes (NPs) of Iraqi Patients
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The inflammatory reactions cause nasal polyposes (NPs), which contained the paranasal sinuses and the nasal mucous membrane. They consist of recurrent multiple masses originating in the paranasal sinuses then spread from the middle meatus to the nasals cavity, which leads to the nasal blockage that causes the restriction of airflow to the olfactory area. This study aims at clarifying the role of IL-12RB2 polymorphism by using PCR technology in nasal mucosal stem cells in nasal polyps of Iraqi patients and use it as a biomarker. Fifty-eight cases of this study are referred to as nasal surgery, which selected from Dept.of Otolaryngology, Baghdad City, Iraq from May 2013 to January 2014. They were grouped into Control group (022 samples

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Publication Date
Tue Apr 01 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of autologous bone marrow-derived stem cells with estimation of molecular events on tooth socket healing in diabetic rabbits (Histological and histomorphometric study)
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Background: Diabetes is a metabolic disorder characterized by chronic hyperglycemia due to an inability to produce insulin. Uncontrolled or poorly controlled diabetes is clinically associated with increased susceptibility to delay healing. Many recent researches have shown that stem cell therapy can be the best choice for treatment of this disease. The aims of this research were investigating regeneration of pancreatic beta cells of diabetic induced rabbits after stem cell transplantation. Materials and Methods: 64 rabbits weighting an average of (2.5 - 3 kg) were used in this experimental study, and divided into 4 groups as follows; group A ( contains 16 healthy rabbits regarded as control group ) , Group B ( contains 16 diabetic rabbits

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Publication Date
Fri Jun 30 2023
Journal Name
Studia Universitatis BabeÈ™-bolyai Chemia
Antitumor and antioxidant potential of majorana hortensis extract binding to the silver nanoparticles on lungs cancer cell line
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Publication Date
Thu Feb 01 2024
Journal Name
Doklady Chemistry
Synthesis, Characterization, and Biological Evaluation of New Cyclic Quinazoline Derivatives as Potential Antibacterial and Antifungal Agents
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Heterocyclic compounds are crucial for medicinal chemistry and the development of therapeutic agents like broad-spectrum antibiotics. This study devised a facile procedure to synthesize novel antimicrobial bicyclic heterocycles from 2-mercapto-3-phenylquinazolin-4(3H)-one. Advanced analytical techniques including 1 H and 13C NMR, elemental analysis, and FT-IR spectroscopy characterized the intricate chemical structures of the products. In vitro assays tested the heterocycles against aerobic and anaerobic bacterial strains using fluconazole and ciprofloxacin as antifungal and antibacterial controls. Results demonstrated the formidable broad-spectrum antibacterial and antifungal activities of the synthesized compounds, with growth inhibition

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Publication Date
Mon Jul 25 2022
Journal Name
International Journal Of Health Sciences
Ca242 as a potential prognostic marker in colorectal cancer Iraqi patients
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Background: Colorectal cancer is the third most common cancer-related mortality worldwide, and its prevalence is increasing among many nations.  Aim of the study: Investigate the predictive value of carbohydrate antigen 242 (CA242) in comparison to the CEA biomarker and to estimate the significance of CA242 as prognosis maker in colorectal cancer patients. Methods: a case-control study with a total of 150 individuals, 100 patients (59 males, 41 females) and 50 healthy controls (26 males, 24 females). using an enzyme-linked immunosorbent (ELISA) to determine the serum levels of CA242 and CEA. The study was carried out at the gastroenterology consultation clinic of the oncology teaching hospital between November 2020 and February

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Publication Date
Tue Apr 30 2024
Journal Name
Iraqi Journal Of Science
Diagnostic Potential Role of CXCL3 and Leptin Levels in Breast Cancer
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The risk of breast cancer development is believed to be attributed to the alterations of a number of key biological components. Within this context, elevated levels of some chemokines that act as growth factors and can promote cancer development. The current study was designed to evaluate CXCL3 (a chemokine C-X-C Motif Ligand 3) and leptin (a peptide hormone synthesized by adipose tissue with cytokine activity) serum of Iraqi breast cancer patients in comparison to healthy controls. A total of 90 participants consisted of 60 patients diagnosed with breast cancer and 30 healthy women as control group were enrolled into this case-control study. Venous blood samples were collected from all participants to evaluate CXCL3 and leptin serum levels

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Publication Date
Wed Jan 10 2024
Journal Name
Nanotechnology
Improving the targeted delivery of curcumin to esophageal cancer cells via a novel formulation of biodegradable lecithin/chitosan nanoparticles with downregulated miR-20a and miR-21 expression
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Abstract<p>Nanoencapsulation, employing safe materials, holds substantial promise for enhancing bioactive compounds’ delivery, stability, and bioactivity. In this study, we present an innovative and safe methodology for augmenting the incorporation of the anticancer agent, curcumin, thereby inducing apoptosis by downregulating miR20a and miR21 expression. Our established methodology introduces three pivotal elements that, to our knowledge, have not undergone formal validation: (1) Novel formulation: We introduce a unique formula for curcumin incorporation. (2) Biocompatibility and biodegradability: our formulation exclusively consists of biocompatible and biodegradable constituents, ensuring t</p> ... Show More
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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Preliminary Pharmacological Evaluation of Esters and Amides Derivatives of Naproxen as Potential Anti-Inflammatory Agents
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4-chloro and 4- nitro substituted phenol and aniline incorporated to a carboxylic group of naproxen a well-known non-steroidal anti-inflammatory drug (NSAID) to increase bulkiness were synthesized for evaluation as  a potential anti-inflammatory agents with expected COX-2 selectivity. In vivo acute anti-inflammatory activity of these compounds (I-IV) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (2.5 mg/Kg) of naproxen. All tested compounds produced a significant reduction in paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, compounds I and IV might show higher effect comparable to that of naproxen and to that of compounds II & III whic

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