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Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine
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With the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabolome and lipidome ofLeishmania donovaniaxenic amastigotes treated with miltefosine. Miltefosine caused a dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid pools, while sphingolipids (SLs) and sterols increased.Leishmania majorpromastigotes devoid of SL biosynthesis through loss of the serine palmitoyl transferase gene (ΔLCB2) were 3-fold less sensitive to miltefosine than wild-type (WT) parasites. Changes in the metabolome and lipidome of miltefosine-treatedL. majormirrored those ofL. donovani. A lack of SLs in the ΔLCB2 mutant was matched by substantial alterations in sterol content. Together, these data indicate that SLs and ergosterol are important for miltefosine sensitivity and, perhaps, MoA.

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Publication Date
Fri Nov 01 2024
Journal Name
Current Medicinal Chemistry
Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR

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Publication Date
Fri Jan 01 2016
Journal Name
Journal University Of Kerbala
Synthesis and Characterization of Some Metal Complexes of [2-chloro-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylcarbamothioyl)acetamide] (L)
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A new ligand [ 2-chloro-N- (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro -1H-pyrazol- 4-ylcarbamothioyl)acetamide](L) was synthesized by reacting the Chloro acetyl isothiocyanate with 4-aminoantipyrine,The ligand was characterized by(C HNS) elemental microanalysis and the spectral measurements including Uv-Vis ,IR ,1H and13C NMR spectra, some transition metals complex of this ligand were prepared and characterized by Uv-Vis, FT-IR spectra, conductivity measurements, magnetic susceptibility and atomic absorption. From the obtained results the molecular formula of all prepared complexes were [M(L)2(H2O)2]Cl2 (M+2 =Mn, Co, Ni, Cu, Zn, Cd and Hg),the proposed geometrical structure for all complexes were octahedral.

Publication Date
Fri Jul 01 2022
Journal Name
Sustainable Materials And Technologies
Green approach for fabrication of graphene from polyethylene terephthalate (PET) bottle waste as reactive material for dyes removal from aqueous solution: Batch and continuous study
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Publication Date
Wed Dec 10 2025
Journal Name
Cell Biochemistry And Biophysics
Green Tea–Driven Green Synthesis of a Curcumin@Platinum Nanohybrid with Multifunctional Antioxidant, Burn-Healing Agent, and Selective Anticancer against PANC-1 Pancreatic Cancer Cells
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This study aimed to fabricate a curcumin@platinum nanohybrid (CUR@Pt NPs) through a green tea–based synthesis method and to evaluate its various functions, including antioxidant, burn-healing, and selective anticancer activities against PANC-1 pancreatic cancer cells. Green tea polyphenols served as natural reducing and stabilizing agents, facilitating an eco-friendly, single-step manufacturing process. Physicochemical characterization confirmed successful nanohybrid formation: a CUR@Pt band appeared at 457 nm in the UV–Vis spectrum, XRD displayed crystalline platinum peaks at 2θ = 46.9°, and 67.0°, matching the (200), and (220) planes, respectively, and TEM images showed well-dispersed spherical nanoparticles with an average siz

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Publication Date
Thu Jan 16 2025
Journal Name
Journal Of Biological Control
Toxicity of polymeric nanocapsules prepared from <i>Moringa oleifera</i> leaf extract against the larvae of <i>Culex pipiens</i> (Diptera: Culicidae)
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The study aimed to prepare a nanocapsules formulation from the acetonic extract of Moringa oleifera leaves, using polymeric capsules, and test its toxicity against the third instar larvae of Culex pipiens mosquitoes. The leaf extract was prepared using acetone as a solvent, and the nano polymeric capsules were prepared using the synthetic polymer polyethylene glycol 4000. The results showed the successful preparation of nano polymeric capsules from the leaf extract, with an average particle size of 259.2 nm, and a nanocapsule diameter of 263.83 nm, as determined by DLS and SEM analysis, respectively. The toxicity results indicated that the nano polymeric capsules of the leaf extract exhibited higher mortality rates, reaching 97.6% a

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Global Pharma Technology
Serum levels of cross-linked n-telopeptide of Type i collagen before and after non-surgical periodontal therapy in type 2 diabetic patients with chronic periodontitis
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Background: Diabetes mellitus is a major risk factor for chronic periodontitis (CP) and hyperglycemia has an important role in the enhancement of the severity of the periodontitis. It has been reported that the progression of CP causes shifting of the balance between bone formation and resorption toward osteoclastic resorption, and this will lead to the release of collagenous bone breakdown products into the local tissues and the systemic circulation. Cross-linked N-telopeptide of type I collagen (NTx) is the amino-terminal peptides of type I collagen which is released during the process of bone resorption. This study was conducted to determine the effects of nonsurgical periodontal therapy on serum level of NTx in type 2 diabetic patients

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Publication Date
Fri May 05 2023
Journal Name
Journal Of Molecular Structure
Synthesis, spectral studies, DFT, biological evaluation, molecular docking and dyeing performance of 1-(4-((2-amino-5-methoxy)diazenyl)phenyl) ethanone complexes with some metallic ions
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Four Co(II), (C1); Ni(II), (C2); Cu(II), (C3) and Zn(II), (C4) chelates have been synthesized with 1-(4-((2-amino- 5‑methoxy)diazenyl)phenyl)ethanone ligand (L). The produced compounds have been identified by using spectral studies, elemental analysis (C.H.N.O), conductivity and magnetic properties. The produced metal chelates were studied using molar ratio as well as sequences contrast types. Rate of concentration (1 ×10􀀀 4 - 3 ×10􀀀 4 Mol/L) sequence Beer’s law. Compound solutions have been noticed height molar absorptivity. The free of ligand and metal chelates had been applied as disperse dyes on cotton fabrics. Furthermore, the antibacterial activity of the produced compounds against various bacteria had been investigated. F

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of The College Of Languages (jcl)
A comparative study of Educational Commonalities in Ibn al-Wardi's Lamiyah and Qaboos- Nameh: مشتركات تعليمى در لاميه ی ابن الوردى و قابوسنامه؛ بررسى مقايسه اى
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A literary-educational work is a work that explains wisdom to the reader and presents moral, educational and instructional issues in a literary form. Qaboos-nameh or Nasihat al-Muluk is an educational and educational book that has a special place in the field of ethics and guidance, where the author guides his children. Also, Ibn al-Wardi's Lamiyah or Nasihat al-Akhwan is a poem containing moral advice and advice in 77 verses that Ibn al-Wardi wrote to his son.

     It seems that the main goal of Ibn al-Wardi and Onsur AL-maali in Lamia and Qaboos-nameh was to express educational and moral issues and spread and convey them to future generations. Ibn al-Wardi, like Onsur AL-maali, listed moral points such as knowledge, humility

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Publication Date
Sat Sep 23 2017
Journal Name
Oriental Journal Of Chemistry
Synthesis and Antioxidant Ability of Some New 6-amino-7H- [1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl) Derivatives Bearing 2,6-Dimethoxy-4-(methoxymethyl)Phenol Moiety
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Compound 4-(((6-amino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)methoxy)methyl)- 2,6-dimethoxyphenol (6) was synthesized by multi steps. The corresponding acetonitrile thioalkyl (7) was cyclized by refluxing with acetic acid to afford 4-(((6-amino-7H-[1,2,4]triazolo[3,4- b][1,3,4]thiadiazin-3-yl)methoxy)methyl)-2,6-dimethoxyphenol (8). Two new series of 4-(((6-(3- (4-aryl)thioureido)-7H-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-3-yl)methoxy)methyl)-2,6- dimethoxyphenol (9a-c) and of 4-(((6-(substitutedbenzamido)7H-[1,2,4]triazolo[3,4- b][1,3,4]thiadiazin-3-yl)methoxy)methyl)-2,6-dimethoxyphenol (10a-c) were synthesized as new derivatives for fused 1,2,4-trizaole-thiadiazine(8). The antioxidants of newly compounds were evaluated by DPPH

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Publication Date
Wed May 10 2017
Journal Name
Journal Of The College Of Languages (jcl)
Procedimientos de traducción de los nombres propios del árabe al español: Fundamentos y Aplicaciones Procedures for translating proper noun from Arabic into Spanish: Fundamentals and Applications
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Los nombres propios nombran a un ser o a un objeto, distinguiéndolo de los demás seres de su misma clase, se escriben siempre con letra mayúscula a principio de palabra. Los lingüistas hacen mayor hincapié en las divergencias de referencia, entre nombres propios y nombres comunes. Así, suele decirse que el sustantivo propio no tiene como referente ningún concepto. El asunto de la traducción  de los nombres propios parecería una cuestión de gusto personal del traductor pero vemos también que en algunas épocas es más frecuente traducirlos, y en otras, por el contrario, se prefiere dejar esos nombres en su forma original, tal vez con algunas adaptaciones ortográficas. Parecería enton­ces cuestión de modas. Pero, eviden

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