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1.
Org Lett ; 22(1): 326-330, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31833772

RESUMO

An NHC-catalyzed cascade cycloaddition reaction is developed for quick access to structurally sophisticated tetrahydrochromeno[4,3-b]pyrrole derivatives. A sterically congested tetrasubstituted chirality carbon center is formed during the cyclization process. All the α-, ß-, and carbonyl carbons of the enal substrates are functionalized in chemo- and stereoselective fashion. The multicyclic chromeno[4,3-b]pyrrole products are generally afforded in good yields with excellent enantio- and diastereoselectivities. Heavily substituted pyrroline derivatives can be afforded from the chiral products through simple protocols.

2.
Diabetes Metab Res Rev ; 35(5): e3142, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30767421

RESUMO

OBJECTIVES: Pancreas steatosis is the description of fat accumulation in the pancreatic gland. The prevalence and development mechanisms of pancreatic steatosis in patients with metabolic disorders still remain unclear. The aim of this study is to systematically review the association between pancreatic steatosis and metabolic co-morbidities. METHODS: We performed a systematic search strategy using three electronic databases (MEDLINE, Scopus, and Embase) for relevant studies concerning the associations of pancreatic steatosis with metabolic syndrome (MetS) and its clinical relevance from inception until 30 September 2018. RESULTS: One thousand three hundred fifty one references were identified in the initial search, and a total of 13 studies involving 49 329 subjects were included. This analyses elucidated the presence of non-alcoholic fatty pancreas disease (NAFPD) and was associated with a significant increased risk of metabolic syndrome (RR = 2.25; 95% CI, 2.00-2.53; P < 0.0001; I2  = 42.8%; eight studies included), hypertension (RR = 1.43; 95% CI, 1.08-1.90; P = 0.013; I2  = 94.7%; nine studies included), non-alcoholic fatty liver disease (NAFLD) (RR = 2.49; 95% CI, 2.06-3.02; P < 0.0001; I2  = 96.9%; nine studies included), diabetes mellitus (RR = 1.99; 95% CI, 1.18-3.35; P = 0.01; I2  = 97.6%; 10 studies included), and central obesity (RR = 1.91; 95% CI, 1.67-2.19; P < 0.0001; I2  = 95.9%; six studies included). The association between NAFPD and hyperlipidaemia was not statistically significant (RR = 1.33; 95% CI, 0.82-2.17; P = 0.249; I2  = 97%; five studies included). CONCLUSIONS: The existing evidence indicates that NAFPD is significantly associated with an increased risk of metabolic syndrome and its components. Well-designed prospective cohort studies between pancreatic steatosis and MetS are needed to elaborate the causality in the future.

3.
J Biomater Sci Polym Ed ; 30(2): 122-136, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30522414

RESUMO

A kind of tumor targeting nitric oxide donor nanoparticle with brushes is described in this paper. The poly(4-vinylphenylboronic acid) polymeric brush, which shows glucose and pH dual responsiveness, endows the ability of hollow S-nitrosothiols nanoparticle to accurate recognition and binding with the sialic acid over-expressed type tumor cells, such as HepG2 and MCF-7 cells. In vitro experiments, including cells capture and release experiments, confocal fluorescence microscope characterization, cytotoxicity assay with different cells, demonstrate the selective recognition and the controlled NO release to kill tumor cells for these S-nitrosothiols nanoparticles. Low concentration of the released NO from the S-nitrosothiols nanoparticles in the transmission would participate physiological activity and avoid serious side effects because the endogenous nature and the physiological necessity to regulate normal biological functions. To the best of our knowledge, this is the first report about polymer nanoparticles as NO donors with functional brushes to selectively identify tumor cells and release NO in a controlled manner.


Assuntos
Antineoplásicos/química , Nanopartículas/química , Doadores de Óxido Nítrico/química , Óxido Nítrico/química , Polímeros/química , S-Nitrosotióis/química , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Ácidos Borônicos/química , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Terapia de Alvo Molecular , Ácido N-Acetilneuramínico/genética , Ácido N-Acetilneuramínico/metabolismo , Óxido Nítrico/efeitos adversos , Óxido Nítrico/farmacologia , Porosidade , Compostos de Vinila/química
4.
Colloids Surf B Biointerfaces ; 173: 356-365, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30316082

RESUMO

It is the goal for the development of cancer target chemotherapy with specific recognition, efficient killing the tumor cells and tissues to avoid the intolerable side effects. Molecular imprinted polymer (MIPs) nanoparticles could introduce kinds of specific bio-markers (template molecules) into the nanoparticles with the subsequent removal, leaving special holes in the structure with predictable recognition specificity with cells. Herein, we design and synthesize a kind of sialic acid (SA) over-expressed tumor target hollow double-layer imprinted polymer nanoparticles with S-nitrosothiols for nitric oxide (NO)-releasing as chemotherapy. Equilibrium/selective bindings properties and probe experimental results implies that the MIPs have an intelligently selective binding to cancer cells featuring high levels of SA glyans, providing precondition for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO-releasing. Cytotoxicity assay with kinds of cells demonstrates the intelligent in vitro SA over-expressed tumor cells targeting recognition, intracellular delivery and cytotoxicity. In vivo bio-distribution in tumor sites and major organs, significant suppression of tumor growth, tumor-bearing mice survival unit, and the systemic toxicity investigation experiments confirm the effective chemotherapy of the S-nitrosothiols MIPs nanoparticles for the target recognition and the controlled NO release for tumor treatment comparing to the results with S-nitrosothiols CPs as delivery system. The inevitable small amount of NO leakage from S-nitrosothiols MIPs would take part in normal physiological activities and not cause serious side effects. For the first time, this kind of nitric oxide based chemotherapy and molecular-imprinting cell recognition technique both in vitro and in vivo, might provide a solution for accurate therapy to various forms of cancer with specific markers and avoid the intolerable side effects of the traditional chemotherapy treatment.


Assuntos
Antineoplásicos/farmacologia , Impressão Molecular/métodos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Pró-Fármacos/farmacologia , S-Nitrosotióis/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Ácidos Borônicos/química , Linhagem Celular Tumoral , Portadores de Fármacos , Coração/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Células MCF-7 , Metacrilatos/química , Camundongos , Camundongos Nus , Nanopartículas/ultraestrutura , Neoplasias/metabolismo , Neoplasias/mortalidade , Neoplasias/patologia , Óxido Nítrico/biossíntese , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , S-Nitrosotióis/química , S-Nitrosotióis/farmacocinética , Ácidos Siálicos/química , Ácidos Siálicos/metabolismo , Baço/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Compostos de Vinila/química , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Org Lett ; 20(2): 333-336, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29286252

RESUMO

Through the incorporation of a silicon atom to an aryl carboxylic ester substrate, the resulting C-Si bond can be activated via the addition of a carbene catalyst on a remote site. This strategy allows for efficient functionalization of the benzylic sp3-carbons of aryl carboxylic esters.

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