Environmental Research, Journal Year: 2024, Volume and Issue: 266, P. 120504 - 120504
Published: Dec. 3, 2024
Language: Английский
Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(9), P. 7260 - 7275
Published: April 23, 2024
Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces fragment-by-fragment growth RL forward and optimization based on low activity lead compound. process integrates fragment growth-based reaction templates, while target docking drug-likeness prediction were simultaneously performed. comprehensive approach considers similarity, internal diversity, synthesizability, effectiveness, thereby enhancing quality efficiency of generation. Finally, series tyrosinase inhibitors generated synthesized. Most compounds exhibited more improved than lead, an optimal candidate compound surpassing effects kojic acid demonstrating significant antipigmentation zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural strategies will play role accelerating discovery improving traditional efficiency.
Language: Английский
Citations
5
BioFactors, Journal Year: 2025, Volume and Issue: 51(1)
Published: Jan. 1, 2025
Abstract Ectoine, a natural bacterial osmolyte, suppressed UVA irradiated‐α‐melanocyte stimulating hormone (MSH) stimulated melanogenesis through antioxidant Nrf2 pathways in human keratinocytes; however, the underlying skin whitening mechanisms were not elucidated. The depigmenting efficiency of Ectoine (0–400 μM) antimelanogenesis and melanin degradation by autophagy promotion was investigated melanoma (B16F10) melanin‐feeding keratinocyte (HaCaT) cells vivo zebrafish model. MTT assay, Western blotting, GFP‐LC3 puncta, AVO formation, immunofluorescence staining, TEM techniques, siLC3 transfection, model utilized. Ectoine‐induced B16F10 HaCaT shown enhanced LC3‐II accumulation, autophagosome autolysosome AVOs ATG4B downregulation, Beclin‐1/Bcl‐2 dysregulation. immunoprecipitation data revealed that increased association between p62 proteins cells. Importantly, NAC pretreatment antagonized diminution inhibited suppressing melanosome gp100, tyrosinase, TRP‐1/‐2, and/or formation via α‐MSH‐stimulated findings displayed melanosome‐engulfing autophagosomes autolysosomes Ectoine‐inhibited reversed with inhibitor 3‐MA or LC3 silencing. In study demonstrated (5 mM) endogenous body pigmentation induction vitro inhibits enhances triggering autophagy. could be utilized as ingredient cosmetic formulations.
Language: Английский
Citations
0
Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 956 - 956
Published: Feb. 19, 2025
L-Theanine, a natural amino acid found in green tea (Camellia sinensis) leaves, is known for its diverse psychotropic effects. This study aimed to evaluate the inhibitory effect of L-theanine on melanin production and uncover regulatory mechanism. We evaluated anti-melanogenic activities vitro vivo. In B16F10 murine melanoma cells induced by α-melanocyte-stimulating hormone, content intracellular tyrosinase activity were determined, melanogenesis-related protein expression signaling pathways analyzed Western blotting. Melanin reduction was further assessed using zebrafish (Danio rerio) test. L-Theanine reduced cells. It also attenuated proteins, such as microphthalmia- associated transcription factor, (TYR), TYR-related protein-1, dopachrome tautomerase. modulated kinase A (PKA), cAMP responder element binding (CREB), phosphorylation of/protein B (Akt), glycogen synthase kinase-3β (GSK-3β), β-catenin. The antimelanogenic (<2 mg/mL) confirmed larvae. inhibited melanogenesis downregulating PKA/CREB Akt/GSK-3β/β-catenin pathways. summary, shows potential skin-whitening compound, warranting investigation possible applications cosmetic pharmaceutical products.
Language: Английский
Citations
0
BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)
Published: Feb. 27, 2025
Melanin pigmentation in oocytes is a critical feature for both the esthetic and developmental aspects of oocytes, influencing their polarity overall development. Despite substantial knowledge melanogenesis melanocytes retinal pigment epithelium cells, molecular mechanisms underlying oocyte remain largely unknown. Here, we compare wild-type, tyr−/− mitf−/− Xenopus tropicalis found that exhibit normal melanin deposition at animal pole, whereas show no this site. Transmission electron microscopy confirmed proceeds normally, similar to wild-type oocytes. Transcriptomic analysis revealed still express melanogenesis-related genes, enabling them complete melanogenesis. Additionally, expression MiT subfamily factor tfe3 relatively high, while tfeb, mitf, tfec levels are extremely low. The pattern tyr other genes. Thus, independent Mitf may be regulated by factors such as Tfe3, which control genes like tyr, dct, tyrp1. Furthermore, transcriptomic data changes related mitochondrial cloud formation represent most significant during Overall, these findings suggest further elucidation Tyr-dependent Mitf-independent pole will enhance our understanding Oogenesis.
Language: Английский
Citations
0
Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108486 - 108486
Published: April 1, 2025
Language: Английский
Citations
0
Industrial Crops and Products, Journal Year: 2025, Volume and Issue: 230, P. 121099 - 121099
Published: April 29, 2025
Language: Английский
Citations
0
Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)
Published: April 29, 2025
2,5-dihydroxyacetophenone, a natural product from the fruiting bodies of Ganoderma cochlear, can effectively and safely inhibit production melanin in zebrafish model. To achieve analogues with more significant inhibition, 9 analogs were synthesised 13 purchased commercially. Among them, 14 compounds production, which 5 displayed most inhibitory effects, rates than 80%, compared to positive control SymWhite®377 (phenylethyl resorcinol). This study elucidated melanin-inhibitory effects 2,5-dihydroxyacetophenone its analogs, providing theoretical foundation for their potential applications anti-melanogenic reagents.
Language: Английский
Citations
0
Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 5333 - 5349
Published: Nov. 1, 2024
Sepsis, a severe condition instigated by infections, continues to be primary global cause of death, typified systemic inflammation and advancing immune dysfunction. Comprehending the complex pathological processes that underlie sepsis is integral creation efficacious treatments. Despite inability animal models entirely reproduce clinical intricacies related sepsis, they are invaluable instruments for exploration development therapeutic approaches. Within this context, zebrafish model particularly noteworthy due its genetic tractability, transparency, appropriateness high-throughput screening mutants compounds. This scholarly review emphasizes crucial role disease plays in enhancing our comprehension exploring applications deciphering inflammatory responses, evaluating consequences alterations, examining novel agents. The Insights derived from research not only augment understanding underlying mechanisms but also possess considerable potential transference these discoveries into therapies, thus potentially transforming approach management. objective article underscore importance realm biomedical pertaining delineate forthcoming opportunities utilizing applications.
Language: Английский
Citations
2
Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)
Published: June 8, 2024
Language: Английский
Citations
1
Algal Research, Journal Year: 2024, Volume and Issue: 82, P. 103601 - 103601
Published: July 2, 2024
Language: Английский
Citations
1