Brief research report: Transcriptional blockade of angiotensin converting enzyme 2 modelled in human retinal pigment epithelial cells DOI Creative Commons
Liam M. Ashander, Amanda L. Lumsden, Yuefang Ma

et al.

Frontiers in Drug Discovery, Journal Year: 2024, Volume and Issue: 4

Published: Oct. 7, 2024

As a key host protein involved in cellular infection by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), angiotensin converting enzyme (ACE)2 is an ideal target for antiviral drugs. Manipulation of transcription provides opportunity graduated blockade that preserves physiological functions. We sought to develop model system evaluating manipulation ACE2 gene using human retinal pigment epithelium. Retinal epithelial cell isolates were prepared from posterior eyecups (n = 11 individual isolates). The cells expressed transcript and protein, expression was not induced hypoxia mimetic dimethyloxaloylglycine, or inflammatory cytokine IL-1β. factors predicted silico cross-referenced with transcriptome, five candidate identified: ETS proto-oncogene 1 factor (ETS1), nuclear I C (NFIC), receptor subfamily 2 group member (NR2C1), TEA domain (TEAD1), zinc finger 384 (ZNF384). candidates individually targeted transfection small interfering (si)RNA. Knockdowns reduced mean all comparison transfected control non-targeted siRNA. Mean under condition NR2C1 knockdown, but ETS1, NFIC, TEAD1, ZNF384 knockdowns. Our findings build on previous work demonstrating potential drugging transcription. Importantly, we show value epithelium as transcriptional blockade, possible approach treating SARS-CoV-2 infection. Brief Research Report.

Language: Английский

Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 Mpro DOI Creative Commons
Jiayi Ren, Zhengfu Zhang, Yi Xia

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 351 - 351

Published: Jan. 16, 2025

The three-year COVID-19 pandemic ‘has’ caused a wide range of medical, social, political, and financial implications. Since the end 2020, various mutations variations in SARS-CoV-2 strains, along with immune escape phenomenon, have emerged. There is an urgent need to identify relatively stable target for development universal vaccines drugs that can effectively combat both strains their mutants. Currently, main focus treating lies disrupting virus’s life cycle. protease (Mpro) closely associated virus replication maturation plays crucial role early stages infection. Consequently, it has become important SARS-CoV-2-specific drugs. This review summarizes recent research progress on novel coronavirus’s proteases, including pivotal Mpro cycle, structure catalytic mechanism Mpro, self-maturation escape, current methods developing antiviral targeting key successfully entered clinical trials. aim provide researchers involved systematic comprehensive information.

Language: Английский

Citations

0
Rifampicin Repurposing Reveals Anti-Melanogenic Activity in B16F10 Melanoma Cells DOI Creative Commons

Y. Terry Lee,

Chang‐Gu Hyun

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 900 - 900

Published: Feb. 15, 2025

Drug repurposing is a cost-effective and innovative strategy for identifying new therapeutic applications existing drugs, thereby shortening development timelines accelerating the availability of treatments. Applying this approach to cosmeceutical ingredients enables creation functional compounds with proven safety efficacy, adding significant value cosmetic industry. This study evaluated potential rifampicin, drug widely used treatment tuberculosis leprosy, as agent. The anti-melanogenic effects rifampicin were assessed in B16F10 melanoma cells, showing no cytotoxicity at concentrations up 40 µM reduction intracellular tyrosinase activity melanin content. Mechanistically, reduced expression melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, via kinase A (PKA)-dependent pathway, leading suppression microphthalmia-associated transcription factor (MITF), which key regulator melanogenesis. Additionally, inhibited p38 signaling pathway but was independent PI3K/protein B (Akt) pathway. Furthermore, it decreased Ser9 phosphorylation, enhancing glycogen synthase kinase-3β (GSK-3β) activity, promoted β-catenin facilitated degradation, collectively contributing inhibition synthesis. To evaluate topical applicability primary human skin irritation tests conducted, adverse observed 20 µM. These findings demonstrate that inhibits melanogenesis through multiple pathways, PKA, MAPKs, GSK-3β/β-catenin. highlights be repurposed agent managing hyperpigmentation disorders, offering valuable insights into novel strategies pigmentation-related conditions.

Language: Английский

Citations

0
Coating of Remdesivir and Ivermectin on Silver Nanoparticles: A Density Functional Theory and Molecular Dynamics Study DOI Creative Commons
Razieh Morad

Results in Surfaces and Interfaces, Journal Year: 2025, Volume and Issue: unknown, P. 100540 - 100540

Published: April 1, 2025

Language: Английский

Citations

0
Brief research report: Transcriptional blockade of angiotensin converting enzyme 2 modelled in human retinal pigment epithelial cells DOI Creative Commons
Liam M. Ashander, Amanda L. Lumsden, Yuefang Ma

et al.

Frontiers in Drug Discovery, Journal Year: 2024, Volume and Issue: 4

Published: Oct. 7, 2024

As a key host protein involved in cellular infection by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), angiotensin converting enzyme (ACE)2 is an ideal target for antiviral drugs. Manipulation of transcription provides opportunity graduated blockade that preserves physiological functions. We sought to develop model system evaluating manipulation ACE2 gene using human retinal pigment epithelium. Retinal epithelial cell isolates were prepared from posterior eyecups (n = 11 individual isolates). The cells expressed transcript and protein, expression was not induced hypoxia mimetic dimethyloxaloylglycine, or inflammatory cytokine IL-1β. factors predicted silico cross-referenced with transcriptome, five candidate identified: ETS proto-oncogene 1 factor (ETS1), nuclear I C (NFIC), receptor subfamily 2 group member (NR2C1), TEA domain (TEAD1), zinc finger 384 (ZNF384). candidates individually targeted transfection small interfering (si)RNA. Knockdowns reduced mean all comparison transfected control non-targeted siRNA. Mean under condition NR2C1 knockdown, but ETS1, NFIC, TEAD1, ZNF384 knockdowns. Our findings build on previous work demonstrating potential drugging transcription. Importantly, we show value epithelium as transcriptional blockade, possible approach treating SARS-CoV-2 infection. Brief Research Report.

Language: Английский

Citations

0