Antisense Oligonucleotides and siRNA as Specific Inhibitors of Gene Expression: Mechanisms of Action and Therapeutic Potential

2008 ◽  
pp. 337-362
Author(s):  
Yvonne Förster ◽  
Bernd Schwenzer
Keyword(s):  
Gene Expression ◽  
Antisense Oligonucleotides ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Specific Inhibitors

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

scholarly journals A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lalit Sharma ◽  
Aditi Sharma ◽  
Ashutosh Kumar Dash ◽  
Gopal Singh Bisht ◽  
Girdhari Lal Gupta
Keyword(s):  
Gene Expression ◽  
Alcohol Withdrawal ◽  
Therapeutic Potential ◽  
Centella Asiatica ◽  
Ethanol Withdrawal ◽  
In Vivo Studies ◽  
Ocimum Sanctum ◽  
Behavioral Parameters ◽  
Gene Expression Studies

Abstract Background Alcohol abuse is a major problem worldwide and it affects people’s health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6–24 h after the last alcohol ingestion. Methods The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals’ free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABAA receptor subunits in the amygdala and hippocampus. Results Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats. Conclusion The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.

Proglucagon-Derived Peptides: Mechanisms of Action and Therapeutic Potential

Physiology ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 357-365 ◽  
Author(s):  
Elaine M Sinclair ◽  
Daniel J. Drucker
Keyword(s):  
Type 2 Diabetes ◽  
Human Disease ◽  
Clinical Relevance ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Receptor Antagonists ◽  
Glucagon Receptor ◽  
Receptor Agonists ◽  
Glucagon Like Peptide

Glucagon is used for the treatment of hypoglycemia, and glucagon receptor antagonists are under development for the treatment of type 2 diabetes. Moreover, glucagon-like peptide (GLP)-1 and GLP-2 receptor agonists appear to be promising therapies for the treatment of type 2 diabetes and intestinal disorders, respectively. This review discusses the physiological, pharmacological, and therapeutic actions of the proglucagon-derived peptides, with an emphasis on clinical relevance of the peptides for the treatment of human disease.

scholarly journals Natural products with therapeutic potential in melanoma metastasis

2015 ◽  
Vol 32 (8) ◽  
pp. 1170-1182 ◽  
Author(s):  
A. AlQathama ◽  
J. M. Prieto
Keyword(s):  
Natural Products ◽  
Cancer Treatment ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Mechanisms Of Action ◽  
Melanoma Metastasis ◽  
Pharmacological Effects ◽  
Cytotoxic Compounds

Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. We here systematically and critically survey more than 30 natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and chart the mechanisms of action for this underexploited property.

scholarly journals The intersectional genetics landscape for human

2019 ◽  
Author(s):  
Andre Macedo ◽  
Alisson M. Gontijo
Keyword(s):  
Gene Expression ◽  
Therapeutic Potential ◽  
Regulatory Element ◽  
Logic Gate ◽  
Cell Types ◽  
Boolean Logic ◽  
Interindividual Variation ◽  
Model Organisms ◽  
Cell Type ◽  
Diagnostic Potential

The human body is made up of hundreds, perhaps thousands of cell types and states, most of which are currently inaccessible genetically. Genetic accessibility carries significant diagnostic and therapeutic potential by allowing the selective delivery of genetic messages or cures to cells. Research in model organisms has shown that single regulatory element (RE) activities are seldom cell type specific, limiting their usage in genetic systems designed to restrict gene expression posteriorly to their delivery to cells. Intersectional genetic approaches can increase the number of genetically accessible cells. A typical intersectional method acts like an AND logic gate by converting the input of two or more active REs into a single synthetic output, which becomes unique for that cell. Here, we systematically assessed the intersectional genetics landscape of human using a curated subset of cells from a large RE usage atlas obtained by Cap Analysis of Gene Expression Sequencing (CAGE-Seq) of thousands of primary and cancer cells (the FANTOM5 consortium atlas). We developed the heuristics and algorithms to retrieve and quality rank AND gate intersections intra- and inter-individually. We find that >90% of the 154 primary cell types surveyed can be distinguished from each other with as little as 3 to 4 active REs, with quantifiable safety and robustness. We call these minimal intersections of active REs with cell-type diagnostic potential “Versatile Entry Codes” (VEnCodes). We show that VEnCodes could be found for 100% of the 158 cancer cell types surveyed, and that most of these are highly robust to intra- and interindividual variation. Our tools for generating and quality-ranking VEnCodes can be adapted to other RE usage databases and to other intersectional methods using alternative Boolean logic operations. Our work demonstrate the potential of intersectional approaches for future gene delivery technologies in human.

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