Development of a new dug is a very lengthy and highly expensive process since only preclinical, pharmacokinetic, pharmacodynamic and toxicological studies include a multiple of in silico, in vitro, in vivo experimentations that traditionally last several years. In the present review, we briefly report some examples that demonstrate the power of the computer-assisted drug discovery process with some examples that are published and revealing the successful applications of artificial intelligence (AI) technology on this vivid area. Besides, we address the situation of drug repositioning (repurposing) in clinical applications. Yet few success stories in this regard that provide us with a clear evidence that AI will reveal its great potential in accelerating effective new drug finding. AI accelerates drug repurposing and AI approaches are altogether necessary and inevitable tools in new medicine development. In spite of the fact that AI in drug development is still in its infancy, the advancements in AI and machine-learning (ML) algorithms have an unprecedented potential. The AI/ML solutions driven by pharmaceutical scientists, computer scientists, statisticians, physicians and others are increasingly working together in the processes of drug development and are adopting AI-based technologies for the rapid discovery of medicines. AI approaches, coupled with big data, are expected to substantially improve the effectiveness of drug repurposing and finding new drugs for various complex human diseases.
- MeSH
- algoritmy MeSH
- lidé MeSH
- objevování léků * MeSH
- strojové učení MeSH
- umělá inteligence * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: Quercetin, a plant flavonoid with potent antioxidant action, has been shown to be ameliorative against different types of liver insults, including D-Galactosamine/Lipopolysaccharide (D-GalN/LPS). The notion that its cytoprotective effects are SIRT1 mediated is still controversial. In this work, we examined whether the synthetic allosteric SIRT1 activator, SRT1720, may similarly attenuate D-GalN/LPS-induced hepatotoxicity. MATERIALS AND METHODS: Male Wistar rats were randomly assigned into 6 groups: (1) Control, (2) Quercetin, (3) SRT1720, (4) D-GalN/LPS, (5) Quercetin + D-GalN/LPS and (6) SRT1720 + D-GalN/LPS. After twenty-four hours, the effects of these treatments were evaluated by biochemical studies, real-time PCR and Western blot. RESULTS: D-GalN/LPS treatment downregulated SIRT1 expression and markedly increased the aminotransferase, bilirubin and conjugated diene levels. Conversely, quercetin and SRT1720 pretreatments upregulated SIRT1 expression and decreased the levels of the aforementioned markers. Quercetin had more profound effect on SIRT1 expression than SRT1720. Moreover, quercetin was more efficacious than SRT1720 in combatting the cytotoxic effects of D-GalN/LPS, as evidenced by lower markers of liver injury. CONCLUSIONS: These results strongly suggest the involvement of SIRT1 in the cytoprotective effects of quercetin and SRT1720 against D-GalN/LPS-induced hepatotoxicity.
- MeSH
- alanintransaminasa metabolismus MeSH
- antioxidancia farmakologie MeSH
- bilirubin metabolismus MeSH
- down regulace účinky léků MeSH
- galaktosamin škodlivé účinky MeSH
- heterocyklické sloučeniny tetra- a více cyklické farmakologie MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lékové postižení jater farmakoterapie MeSH
- lipopolysacharidy škodlivé účinky MeSH
- náhodné rozdělení MeSH
- potkani Wistar MeSH
- quercetin farmakologie MeSH
- sirtuin 1 metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- bioreaktory MeSH
- financování organizované MeSH
- hepatocyty MeSH
- krysa rodu rattus MeSH
- laboratorní zvířata MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
- techniky in vitro MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
The aim of our study was to evaluate the efficacy of FK506, mycophenolate mofetil (MM) and aminoguanidine (AMG) on infiltration of macrophages (MPHs), neutrophils (NPHs) and dendritic cells (DC) into corneal grafts during the early phases after transplantation (Tx). Tx was performed in mice (C57BL/10 to BALB/c). Therapy included FK506 (0.2 mg/kg), MM (30 mg/kg) or AMG (0.1 g/kg), started at the day of Tx and was injected i.p. daily. Corneas were excised on the 3rd and 7th day after Tx. Immunohistological evaluation using antibodies against MPHs, NPHs and DC was performed and corneal grafts were assessed in the periphery and in central part of the cornea separately. On the 3rd day after Tx, a massive infiltration of MPHs and NPHs into corneal grafts was revealed; the DC infiltration was lower in all treated groups. Treatment with FK506 and MM led to a significant reduction of NPHs in the centers of the grafts, but not of MPHs. In contrast, AMG significantly reduced MPHs migration into allografts on the third day after Tx, whereas NPHs infiltration has not been attenuated. However, immunosuppressants had no influence on the infiltration of DC during early phases after Tx.
- MeSH
- dendritické buňky účinky léků MeSH
- financování organizované využití MeSH
- guanidiny farmakokinetika terapeutické užití MeSH
- imunosupresiva farmakokinetika farmakologie imunologie MeSH
- kyselina mykofenolová analogy a deriváty farmakokinetika terapeutické užití MeSH
- makrofágy účinky léků MeSH
- myši inbrední BALB C chirurgie imunologie MeSH
- myši inbrední C57BL chirurgie imunologie MeSH
- takrolimus farmakokinetika farmakologie terapeutické užití MeSH
- transplantace rohovky imunologie metody MeSH
- MeSH
- biotransformace MeSH
- krysa rodu rattus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- hypoxie MeSH
- játra MeSH
- nitroprusid škodlivé účinky MeSH
- oxidy dusíku MeSH
- Publikační typ
- techniky in vitro MeSH
- MeSH
- galaktosamin škodlivé účinky MeSH
- hypoxie MeSH
- játra patologie MeSH
- nitroprusid metabolismus MeSH
- oxid dusnatý MeSH
- Publikační typ
- techniky in vitro MeSH
