scholarly journals Oligonucleotide–Palladacycle Conjugates as Splice-Correcting Agents

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1180 ◽  
Author(s):  
Madhuri Hande ◽  
Osama Saher ◽  
Karin Lundin ◽  
C. Smith ◽  
Rula Zain ◽  
...  
Keyword(s):  
Human Liver ◽  
Therapeutic Agents ◽  
Target Sequence ◽  
Modified Oligonucleotides ◽  
Reporter Cell ◽  
Melting Temperatures ◽  
Human Osteosarcoma ◽  
Uv Melting ◽  
Melting Experiments ◽  
Human Cervical Cancer

2’-O-Methylribo phosphorothioate oligonucleotides incorporating cyclopalladated benzylamine conjugate groups at their 5’-termini have been prepared and their ability to hybridize with a designated target sequence was assessed by conventional UV melting experiments. The oligonucleotides were further examined in splice-switching experiments in human cervical cancer (HeLa Luc/705), human liver (HuH7_705), and human osteosarcoma (U-2 OS_705) reporter cell lines. Melting temperatures of duplexes formed by the modified oligonucleotides were approximately 5 °C lower than melting temperatures of the respective unmodified duplexes. The cyclopalladated oligonucleotides functioned as splice-correcting agents in the HeLa Luc/705 cell line somewhat more efficiently than their unmodified counterparts. Furthermore, the introduction of this chemical modification did not induce toxicity in cells. These results demonstrate the feasibility of using covalently metalated oligonucleotides as therapeutic agents.

scholarly journals Recovery of Aluminum from Industrial Waste (Slag) by Melting and Electrorefining Processes

2018 ◽  
Vol 14 (3) ◽  
pp. 81-91 ◽  
Author(s):  
Maytham Mahmood Ali ◽  
Rabiha Saleh Yassen
Keyword(s):  
Slag Sample ◽  
Melting Process ◽  
Industrial Wastes ◽  
Aluminum Production ◽  
Economic Returns ◽  
Secondary Aluminum ◽  
X Ray ◽  
Melting Temperatures ◽  
Salt Slag ◽  
Melting Experiments

Slag of aluminum is a residue which results during the melting process of primary and secondary aluminum production. Salt slag of aluminum is hazardous solid waste according to the European Catalogue for Hazardous Wastes. Hence, recovery of aluminum not only saves the environment, but also has advantages of financial and economic returns. In this research, aluminum was recovered and purified from the industrial wastes generated as waste from both of State Company for Electrical and Electronic Industries (Baghdad/AlWaziriya) and General Company for Mechanical Industries (Babylon/-Al-Escandria). It was found that these wastes contain tiny proportions of other elements such as iron, copper, nickel, titanium, lead, and potassium. Wastes were recovered for green sustainability, saving energy and cost effectiveness. The method applied for recovering aluminum was pyro-metallurgical method by smelting and refining. X-Ray fluorescence spectroscopy and X- Ray diffraction techniques of the slag sample were used to determine the chemical analysis and phases, respectively. Melting experiments were conducted by using different types of fluxes (KAlF4, NaCl, KCl and AlCl3) at different percentages (0, 5, 10 %) and different melting temperatures (700, 750, 800oC). Design of Experiment (DOE) by Taguchi method, orthogonal array L9, was used in melting experiments. Melting efficiency of aluminum was equal to 84.7%. Electro-refining of aluminum was done by using anhydrous aluminum chloride and NaCl as ionic liquids at low temperature 100 ◦C in electro-refining method producing aluminum of 99% purity.                                  

scholarly journals Development of Cellular Models to Study Efficiency and Safety of Gene Edition by Homologous Directed Recombination Using the CRISPR/Cas9 System

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1492
Author(s):  
Sabina Sánchez-Hernández ◽  
Araceli Aguilar-González ◽  
Beatriz Guijarro-Albaladejo ◽  
Noelia Maldonado-Pérez ◽  
Iris Ramos-Hernández ◽  
...  
Keyword(s):  
Cell Lines ◽  
Main Concern ◽  
Target Sequence ◽  
Gene Repair ◽  
Reporter Cell ◽  
Delivery Method ◽  
Cellular Models ◽  
Target Sites ◽  
Reporter Systems ◽  
Or Gene

In spite of the enormous potential of CRISPR/Cas in basic and applied science, the levels of undesired genomic modifications cells still remain mostly unknown and controversial. Nowadays, the efficiency and specificity of the cuts generated by CRISPR/Cas is the main concern. However, there are also other potential drawbacks when DNA donors are used for gene repair or gene knock-ins. These GE strategies should take into account not only the specificity of the nucleases, but also the fidelity of the DNA donor to carry out their function. The current methods to quantify the fidelity of DNA donor are costly and lack sensitivity to detect illegitimate DNA donor integrations. In this work, we have engineered two reporter cell lines (K562_SEWAS84 and K562GWP) that efficiently quantify both the on-target and the illegitimate DNA donor integrations in a WAS-locus targeting setting. K562_SEWAS84 cells allow the detection of both HDR-and HITI-based donor integration, while K562GWP cells only report HDR-based GE. To the best of our knowledge, these are the first reporter systems that allow the use of gRNAs targeting a relevant locus to measure efficacy and specificity of DNA donor-based GE strategies. By using these models, we have found that the specificity of HDR is independent of the delivery method and that the insertion of the target sequence into the DNA donor enhances efficiency but do not affect specificity. Finally, we have also shown that the higher the number of the target sites is, the higher the specificity and efficacy of GE will be.

scholarly journals Recovery of Aluminum from Industrial Waste (Slag) by Melting and Electrorefining Processes

2018 ◽  
Vol 14 (3) ◽  
pp. 81-91
Author(s):  
Maytham Mahmood Ali ◽  
Rabiha Saleh Yassen
Keyword(s):  
Slag Sample ◽  
Melting Process ◽  
Industrial Wastes ◽  
Aluminum Production ◽  
Economic Returns ◽  
Secondary Aluminum ◽  
X Ray ◽  
Melting Temperatures ◽  
Salt Slag ◽  
Melting Experiments

Slag of aluminum is a residue which results during the melting process of primary and secondary aluminum production. Salt slag of aluminum is hazardous solid waste according to the European Catalogue for Hazardous Wastes. Hence, recovery of aluminum not only saves the environment, but also has advantages of financial and economic returns. In this research, aluminum was recovered and purified from the industrial wastes generated as waste from both of State Company for Electrical and Electronic Industries (Baghdad/AlWaziriya) and General Company for Mechanical Industries (Babylon/-Al-Escandria). It was found that these wastes contain tiny proportions of other elements such as iron, copper, nickel, titanium, lead, and potassium. Wastes were recovered for green sustainability, saving energy and cost effectiveness. The method applied for recovering aluminum was pyro-metallurgical method by smelting and refining. X-Ray fluorescence spectroscopy and X- Ray diffraction techniques of the slag sample were used to determine the chemical analysis and phases, respectively. Melting experiments were conducted by using different types of fluxes (KAlF4, NaCl, KCl and AlCl3) at different percentages (0, 5, 10 %) and different melting temperatures (700, 750, 800oC). Design of Experiment (DOE) by Taguchi method, orthogonal array L9, was used in melting experiments. Melting efficiency of aluminum was equal to 84.7%. Electro-refining of aluminum was done by using anhydrous aluminum chloride and NaCl as ionic liquids at low temperature 100 ◦C in electro-refining method producing aluminum of 99% purity.                                  

scholarly journals Hepatotoxicity: Treatment, causes and applications of medicinal plants as therapeutic agents

2017 ◽  
Vol 6 (3) ◽  
pp. 186-193
Author(s):  
Meagan Thompson ◽  
◽  
Yogini Jaiswal ◽  
Ilya Wang ◽  
Leonard Williams ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Liver Damage ◽  
Metabolic Pathways ◽  
Human Liver ◽  
Pharmaceutical Compounds ◽  
Therapeutic Agents ◽  
Pharmaceutical Drugs ◽  
Active Components ◽  
Oxidation Reduction ◽  
Hepatoprotective Agents

Hepatotoxicity, or liver damage, is caused by hepatotoxins, which may source from chemicals, dietary supplements, pharmaceutical drugs, and medicinal plants. Notably, numerous medicinal plants are used to alleviate illness, particularly in traditional systems of medicine, such as Ayurveda and Traditional Chinese Medicine. These systems of medicine have been implemented for centuries for treating various ailments. Some medicinal plants serve as hepatoprotectors against liver damage, while others induce hepatotoxicity. Recent advances in instrumentation and knowledge of active components have allowed research scientists to study the drug metabolic pathways of these phytopharmaceuticals to establish a causal relationship between medicinal plants and their pharmacological effects on the human liver, as a hepatoprotector or a causative agent for hepatotoxicity. The human liver metabolizes substances via oxidation, reduction, hydration, hydrolysis, condensation, conjugation, or isomerization. Interruption of these processes can lead to hepatotoxicity, causing liver cancer, cirrhosis and Hepatitis C, respectively. Such diseases are responsible for higher mortality rates worldwide. The present review focuses on highlighting various plants that are hepatoprotective, hepatotoxic and the challenges faced by phytopharmaceuticals. The article also emphasizes on various agents (bioactives from medicinal plants, industrial toxins and pharmaceutical compounds) that have been reported to cause hepatotoxicity. The article proposes views and beneficial medicinal plants that can help in identification of natural hepatoprotective agents for future natural product based drug discovery.

scholarly journals Synthesis of Oligonucleotides Containing 2′-N-alkylaminocarbonyl-2′-amino-LNA (2′-urea-LNA) Moieties Using Post-Synthetic Modification Strategy

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 346 ◽  
Author(s):  
Shoko Yamashita ◽  
Kodai Nishida ◽  
Takashi Osawa ◽  
Ayumi Nakanishi ◽  
Yuta Ito ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Room Temperature ◽  
Uv Melting ◽  
Oligonucleotide Conjugates ◽  
Melting Experiments ◽  
Powerful Strategy ◽  
Substituted Urea

The post-synthetic modification of an oligonucleotide is a powerful strategy for the synthesis of various analogs of the oligonucleotide, aiming to achieve the desired functions. In this study, we synthesized the thymidine phosphoramidite of 2′-N-pentafluorophenoxycarbonyl-2′-amino-LNA, which was introduced into oligonucleotides. Oligonucleotides containing a 2′-N-pentafluorophenoxycarbonyl-2′-amino-LNA unit could be isolated under ultra-mild deprotection conditions (50 mM K2CO3 in MeOH at room temperature for 4 h). Moreover, by treatment with various amines as a post-synthetic modification, the oligonucleotides were successfully converted into the corresponding 2′-N-alkylaminocarbonyl-2′-amino-LNA (2′-urea-LNA) derivatives. The duplex- and triplex-forming abilities of the synthesized oligonucleotides were evaluated by UV-melting experiments, which showed that 2′-urea-LNAs could stabilize the nucleic acid complexes, similar to the proto-type, 2′-amino-LNA. Thus, 2′-urea-LNAs could be promising units for the modification of oligonucleotides; the design of a substituent on urea may aid the formation of useful oligonucleotides. In addition, pentafluorophenoxycarbonyl, an amino moiety, acted as a precursor of the substituted urea, which may be applicable to the synthesis of oligonucleotide conjugates.

Water-soluble amphiphilic ruthenium(ii) polypyridyl complexes as potential light-activated therapeutic agents

2020 ◽  
Vol 56 (65) ◽  
pp. 9332-9335
Author(s):  
Sandra Estalayo-Adrián ◽  
Salvador Blasco ◽  
Sandra A. Bright ◽  
Gavin J. McManus ◽  
Guillermo Orellana ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Therapeutic Agents ◽  
Water Soluble ◽  
Polypyridyl Complexes ◽  
Cervical Cancer Cells

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.

Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

2020 ◽  
Vol 134 (12) ◽  
pp. 1403-1432 ◽  
Author(s):  
Manal Muin Fardoun ◽  
Dina Maaliki ◽  
Nabil Halabi ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Therapeutic Agents ◽  
Adipose Tissue Inflammation ◽  
Cellular Mechanisms ◽  
Tissue Inflammation ◽  
Cholesterol Levels ◽  
Naturally Occurring ◽  
Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes

Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cytochrome P450 2A6
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