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siRNA drug delivery across the blood-brain barrier in Alzheimer's Disease
Adv Drug Deliv Rev. 2023 Jun 21:114968. doi: 10.1016/j.addr.2023.114968. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challeng...
Source: Advanced Drug Delivery Reviews - June 23, 2023 Category: Drugs & Pharmacology Authors: Muhammad Imran Sajid Fahad Sultan Sheikh Faiza Anis Nourina Nasim Rachita K Sumbria Surya M Nauli Rakesh Kumar Tiwari Source Type: research

Characterization of Positively Charged Polyplexes by Tunable Resistive Pulse Sensing.
This article describes a new coating solution based on choline-chloride. Coating is verified by current-voltage (I-V) recordings and ultimately tested on a positively charged nanoparticle formulation comprising of siRNA and PEG-PCL-PEI polymer. This coating allows successful size, polydispersity index (PDI) and concentration measurement by tunable resistive pulse sensing of positively charged PEI-based polyplexes. This article provides the foundation for further characterization of polyplexes as well as other positively charged nanoparticle formulations based on particle by particle measurements. PMID: 33338601 [PubMe...
Source: European Journal of Pharmaceutics and Biopharmaceutics - December 15, 2020 Category: Drugs & Pharmacology Authors: Wm Keil T, Merkel OM Tags: Eur J Pharm Biopharm Source Type: research

miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

The NCATS BioPlanet – An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics
We report here the construction, features, and utilization of a comprehensive integrated and non-redundant pathway resource, the NCATS BioPlanet (Figure 1). The resource hosts information only from public sources that have been herein further manually curated to ensure the quality of the data. Along with our pathway warehouse, the NCATS BioPlanet software platform allows easy browsing and visualization of the universe of pathways, and exploration of associations among them. Additionally, we curated the set of annotated pathways in terms of the biological space covered and the current availability of assays, either commerci...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2
Conclusion We report the discovery that ZEB1-AS1 functionally participates in ox-LDL-induced ECs injury via LRPPRC-mediated stabilization of NOD2. Uncovering the precise role of ZEB1-AS1/LRPPRC/NOD2 pathway in the progression of ox-LDL-induced ECs death and AS will not only increase our knowledge of ox-LDL-induced AS, but also enable the development of novel therapeutic strategies to overcome oxidation product-induced diseases. Author Contributions XX and CL designed and mainly did the study. CM, ZD, and YD helped and did the study. Conflict of Interest Statement The authors declare that the research was conducted in ...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

The involvement of miR-155 in blood pressure regulation in pregnant hypertension rat via targeting FOXO3a.
CONCLUSIONS: The inhibition of miR-155 improves the damage of pregnant hypertension via the upregulation of FOXO3a, which provides academic leads for the future therapy of pregnant hypertension. PMID: 30402830 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - November 9, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

DUSP facilitates RPMI8226 myeloma cell aging and inhibited TLR4 expression.
CONCLUSIONS: DUSP facilitates H2O2-induced aging of myeloma cell line RPMI8226 and suppresses TLR4 expression, which provides academic basis for clinical intervention. PMID: 30280787 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - October 5, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

The regulatory role of SLP-2 and mechanism on CCBE1 gene expression in rectal carcinoma and adjacent lymphatic tube tissues.
CONCLUSIONS: SLP-2 is up-regulated in RC lymphatic tissues, and is positively correlated with the level of CCBE1, which provides the academic the basis for the development of medicine targeting SLP-2 in the anti-rectal carcinoma therapy. PMID: 29364474 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - January 26, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Design and delivery of therapeutic siRNAs: application to MERS-Coronavirus.
CONCLUSION: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, an effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV. PMID: 29119921 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - November 8, 2017 Category: Drugs & Pharmacology Authors: Sohrab SS, El-Kafrawy SA, Mirza Z, Kamal MA, Azhar EI Tags: Curr Pharm Des Source Type: research

Current preclinical small interfering RNA (siRNA)-based conjugate systems for RNA therapeutics.
Abstract Recent promising clinical results of RNA therapeutics have drawn big attention of academia and industries to RNA therapeutics and their carrier systems. To improve their feasibility in clinics, systemic evaluations of currently available carrier systems under clinical trials and preclinical studies are needed. In this review, we focus on recent noticeable preclinical studies and clinical results regarding siRNA-based conjugates for clinical translations. Advantages and drawbacks of siRNA-based conjugates are discussed, compared to particle-based delivery systems. Then, representative siRNA-based conjugate...
Source: Advanced Drug Delivery Reviews - October 27, 2015 Category: Drugs & Pharmacology Authors: Lee SH, Kang YY, Jang HE, Mok H Tags: Adv Drug Deliv Rev Source Type: research