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1.
Int J Ophthalmol ; 16(9): 1431-1440, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724282

RESUMO

AIM: To explore the latest application of artificial intelligence (AI) in optical coherence tomography (OCT) images, and to analyze the current research status of AI in OCT, and discuss the future research trend. METHODS: On June 1, 2023, a bibliometric analysis of the Web of Science Core Collection was performed in order to explore the utilization of AI in OCT imagery. Key parameters such as papers, countries/regions, citations, databases, organizations, keywords, journal names, and research hotspots were extracted and then visualized employing the VOSviewer and CiteSpace V bibliometric platforms. RESULTS: Fifty-five nations reported studies on AI biotechnology and its application in analyzing OCT images. The United States was the country with the largest number of published papers. Furthermore, 197 institutions worldwide provided published articles, where University of London had more publications than the rest. The reference clusters from the study could be divided into four categories: thickness and eyes, diabetic retinopathy (DR), images and segmentation, and OCT classification. CONCLUSION: The latest hot topics and future directions in this field are identified, and the dynamic evolution of AI-based OCT imaging are outlined. AI-based OCT imaging holds great potential for revolutionizing clinical care.

2.
Chem Commun (Camb) ; 55(87): 13066-13069, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31570904

RESUMO

A platinum(ii) complex containing an aminophosphonate ligand preferentially accumulates in the endoplamic reticulum (ER) in association with potent ER stress and reactive oxygen species generation, followed by the activation of damage-associated molecular pattern signals and immune responses. Importantly, the Pt complex exhibits potent anti-tumour activities in two independent mouse models via an immunogenic cell death pathway.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Ésteres/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Organofosfonatos/farmacologia , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos Imunológicos/química , Morte Celular/efeitos dos fármacos , Ésteres/química , Humanos , Ligantes , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Organofosfonatos/química , Compostos Organoplatínicos/química
3.
Free Radic Biol Med ; 129: 418-429, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30266678

RESUMO

Agents with multiple modes of tumor cell death can be effective chemotherapeutic drugs. One example of a bimodal chemotherapeutic approach is an agent that can induce both apoptosis and autophagic death. Thus far, no clinical anticancer drug has been shown to simultaneously induce both these pathways. Mono-functional platinum complexes are potent anticancer drug candidates which act through mechanisms distinct from cisplatin. Here, we describe the synthesis and characterize of two mono-functional platinum complexes containing 8-substituted quinoline derivatives as ligands. In comparison to cisplatin, n-Mon-Pt-1 exhibited a greater in vitro cytotoxicity, was more effective in resistant cells and elicited a better anticancer effect. Mechanistic experiments indicate that n-Mon-Pt-1 mainly accumulates in mitochondria, and stimulates significant TrxR inhibition, ROS release and an ER stress response, ultimately resulting in a simultaneous induction of apoptosis and autophagy. Importantly, compared to cisplatin, n-Mon-Pt-1 exhibits lower acute toxicity and better anticancer activity in a murine tumor model.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Células A549 , Animais , Antineoplásicos/síntese química , Apoptose/genética , Autofagia/genética , Linhagem Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Compostos Organoplatínicos/síntese química , Quinolinas/química , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Tiorredoxina Redutase 1/genética , Tiorredoxina Redutase 1/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
4.
Eur J Med Chem ; 155: 639-650, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29935437

RESUMO

Agents with multiple modes of tumor cell death can be effective chemotherapeutic drugs. One example of a bimodal chemotherapeutic approach is an agent that can induce both apoptosis and autophagic death. Thus far, no clinical anticancer drug has been shown to simultaneously induce both these pathways. Mono-functional platinum complexes are potent anticancer drug candidates which act through mechanisms distinct from cisplatin. Here, we describe the synthesis and characterize of two mono-functional platinum complexes containing 8-substituted quinoline derivatives as ligands, [PtL1Cl]Cl [L1 = (Z)-1-(pyridin-2-yl)-N-(quinolin-8-ylmethylene) methanamine] (Mon-Pt-1) and [PtL2Cl]Cl [L2 = (Z)-2-(pyridin-2-yl)-N-(quinolin-8-ylmethylene) ethanamine] (Mon-Pt-2). In comparison to cisplatin, Mon-Pt-2 exhibited a greater in vitro cytotoxicity, was more effective in resistant cells and elicited a better anticancer effect. Mechanistic experiments indicate that Mon-Pt-2 mainly accumulates in mitochondria, and stimulates significant TrxR inhibition ROS release and an ER stress response, mediated by mitochondrial dysfunction, ultimately resulting in a simultaneous induction of apoptosis and autophagy. Importantly, compared to cisplatin, Mon-Pt-2 exhibits lower acute toxicity and better anticancer activity in a murine tumor model. To the best of our knowledge, Mon-Pt-2 is the first mono-functional platinum complex inducing pro-death autophagy and apoptosis of cancer cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Relação Estrutura-Atividade
5.
J Med Chem ; 61(8): 3478-3490, 2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29606001

RESUMO

Agents inducing both apoptosis and autophagic death can be effective chemotherapeutic drugs. In our present work, we synthesized two organometallic gold(III) complexes harboring C^N ligands that structurally resemble tetrahydroisoquinoline (THIQ): Cyc-Au-1 (AuL1Cl2, L1 = 3,4-dimethoxyphenethylamine) and Cyc-Au-2 (AuL2Cl2, L2 = methylenedioxyphenethylamine). In screening their in vitro activity, we found both gold complexes exhibited lower toxicity, lower resistance factors, and better anticancer activity than those of cisplatin. The organometallic gold(III) complexes accumulate in mitochondria and induce elevated ROS and an ER stress response through mitochondrial dysfunction. These effects ultimately result in simultaneous apoptosis and autophagy. Importantly, compared to cisplatin, Cyc-Au-2 exhibits lower toxicity and better anticancer activity in a murine tumor model. To the best of our knowledge, Cyc-Au-2 is the first organometallic Au(III) compound that induces apoptosis and autophagic death. On the basis of our results, we believe Cyc-Au-2 to be a promising anticancer agent or lead compound for further anticancer drug development.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Tetra-Hidroisoquinolinas/farmacologia , Células A549 , Adenocarcinoma Bronquioloalveolar/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/uso terapêutico , Complexos de Coordenação/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Masculino , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/uso terapêutico , Tetra-Hidroisoquinolinas/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
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