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1.
Nanomedicine (Lond) ; 14(19): 2595-2611, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31361188

RESUMO

Aim: To improve the retention of fluorescein sodium (FS) as a kind of clinical contrast agent for fundus fluorescein angiography (FFA). Materials & methods: Polyethyleneimine (PEI) was designed to synthesize PEI-NHAc-FS nanoparticles (NPs), and the formed NPs were characterized by both physicochemical properties and their effects on FFA. Results: Compared with free FS, PEI-NHAc-FS NPs showed similar optical performance, and could obviously reduce cellular adsorption and uptake both in vitro and in vivo, which could promote the metabolism of NPs in ocular blood vessels. Conclusion: PEI-NHAc-FS NPs represent a smart nanosize fluorescence contrast agent, which hold promising potential for clinical FFA diagnosis, therapy and research work.

2.
J Transl Med ; 17(1): 46, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30767763

RESUMO

BACKGROUND: Although previous prevalence studies of DED were reported from some countries worldwide, national data are unavailable in China. We aimed to conduct an up-to-date national survey on the prevalence of DED in China and find out the potential risk factors including air pollutant. METHODS: 23,922 eligible outpatients were recruited from ophthalmic clinics of 32 cities in China in 2013 by registration orders. The patients' demographic characteristics, history of keratorefractive surgery, diseases and medication history were collected and the daily air pollutant data in 2013. Multivariate logistic analysis was performed to identify the potential risk factors associated with DED. The association between related factors and dry eye diseases subtypes evaluated as p value and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Among 23,922 outpatients, the prevalence of DED was 61.57%, and that of the male patients was 57.64% and of the female was 65.32% (P < 0.0001). Multivariate logistic regression suggested that the possible risk factors for DED included: female, older age, history of keratorefractive surgery, presence of arthritis, thyroid diseases, and antihistamine, diuretic, duodenal ulcer drugs, diazepam. Air pollutants including O3, PM2.5, and SO2 were also identified as the risk factors. CONCLUSION: The prevalence of DED among ophthalmic outpatients in China was considerably high. Age, gender, history of keratorefractive surgery, diseases, medication history, and air pollutants were associated with DED prevalence.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30508538

RESUMO

BACKGROUND: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinical efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal, phase III trials for registration. OBJECTIVE: To investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 AUN/ml) in birch pollen allergic adult patients. METHODS: A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted in 406 adult patients with moderate to severe birch pollen induced allergic rhinoconjunctivitis with or without mild to moderate controlled asthma. Treatment was started 3-6 months prior to the birch pollen season and was continued during the season in 40 clinical study centers in 5 European countries. For primary endpoint assessment the recommended combined symptom and medication score (CSMS) of the European Academy of Allergy and Clinical Immunology (EAACI) was used. Secondary endpoints included Quality of Life assessments, immunological parameter and safety. RESULTS: The primary efficacy results demonstrate a significant (p< 0.0001) and clinically relevant (32%) reduction in the CSMS compared to placebo after 3-6 months of SLIT. Significant better rhinoconjunctivitis quality of life scores (p<0.0001) and patients' own overall assessment of their health status: visual analogue scale (EQ-VAS; p=0.0025) were also demonstrated. In total, a good safety profile of SLIT was observed. CONCLUSION: This study confirmed clinical efficacy as well as safety of a sublingual liquid birch pollen extract in birch pollen allergic adult patients in a pivotal phase III trial. (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307).

4.
Drug Des Devel Ther ; 12: 4149-4161, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30584279

RESUMO

Purpose: The purpose of this study was to evaluate the effect and mechanism of quercetin on TGF-ß1-induced retinal pigment epithelial (RPE) cell proliferation, migration, and extracellular matrix secretion. Materials and methods: Cell counting kit-8, transwell, wound-healing assays, and ELISA were used to assess viability, migration, and collagen I secretion, respectively. Western blot analysis and qPCR were employed to detect mRNA and protein expression levels, respectively. Results: Quercetin suppressed TGF-ß1-induced cell proliferation, migration, and collagen I secretion. The results also showed that mRNA and protein expression of epithelial-mesenchymal transition (EMT)-related markers such as alpha-smooth muscle actin and N-cadherin was downregulated by quercetin in TGF-ß1-treated RPE cells; conversely, quercetin upregulated the expression of E-cadherin and tight junction protein 1 (ZO-1). In addition, quercetin could inhibit mRNA and protein expression of matrix metalloproteinases. Quercetin may reverse the progression of EMT via the Smad2/3 pathway. Conclusion: Our results demonstrate the protective effects of quercetin on RPE cell EMT, revealing a potential therapeutic agent for proliferative vitreoretinopathy treatment.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Quercetina/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Actinas/genética , Actinas/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fosforilação , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Proteína Smad4/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
5.
Drug Des Devel Ther ; 12: 2715-2730, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233136

RESUMO

Purpose: This study aimed to assess the effects of 17ß-estradiol (ßE2) on blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans and elucidate the protective mechanism of ßE2 underlying these processes. Methods: Female ovariectomized (OVX) rats were intravitreally injected with ßE2 before blue LED exposure (3,000 lux, 2 hours). Retinal function and morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. Gene expression and protein expression were quantified using quantitative real-time RT-PCR, Western blotting, and immunohistochemistry. Autophagosomes were examined by electron microscopy. Results: Female OVX rats were exposed to blue LED, inducing RD. ßE2 significantly prevented the reduction in the a- and b-wave ERG amplitudes and the disruption of retinal structure, the loss of photoreceptor cells, and the decrease in the thickness of the outer nuclear layer caused by blue LED exposure. ßE2 also decreased cell apoptosis in the retina in blue LED-induced RD. Additionally, ßE2 reduced ROS levels and apoptosis in H2O2-treated human retinal pigment epithelial (ARPE-19) cells. Furthermore, ßE2 increased the protein expression of p-Akt and Bcl-2 and decreased the protein expression of cleaved caspase-3 and Bax during blue LED-induced retinal damage and in H2O2-treated ARPE-19 cells. ßE2 also increased the number of autopha-gosomes and upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes. Conclusion: ßE2 protects against blue LED-induced RD and H2O2-induced oxidative stress by acting as an antioxidant, and its protective mechanism might occur by reducing apoptosis and enhancing autophagy; ßE2 may be a novel and effective therapy for age-related macular degeneration.

6.
J Neurol Neurosurg Psychiatry ; 89(6): 618-626, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29326294

RESUMO

OBJECTIVES: The clinical and epidemiological profiles of Guillain-Barré syndrome (GBS) in southern China have yet to be fully recognised. We aimed to investigate the subtypes of GBS in southern China, compare the clinical features of demyelinating form with that of axonal form and test whether preceding infections and age have influence on the clinical phenotype, disease course and severity of GBS. METHODS: Medical records of patients with a diagnosis of GBS admitted to 31 tertiary hospitals, located in 14 provinces in southern China, from 1 January 2013 to 30 September 2016, were collected and retrospectively reviewed. RESULTS: Finally. 1056 patients, including 887 classic GBS and 169 variants, were enrolled. The 661 classic patients with available electromyographic data were grouped as having acute inflammatory demyelinating polyneuropathy (AIDP, 49.0%), acute motor axonal neuropathy (AMAN, 18.8%), inexcitable (0.9%) and equivocal (31.3%). In contrast to AIDP, patients with AMAN were characterised by earlier nadir (P=0.000), higher Hughes score at nadir (P=0.003) and at discharge (P=0.000). Preceding upper respiratory infections were identified in 369 (34.9%) patients, who were more inclined to develop AIDP (P=0.000) and Miller-Fisher syndrome (P=0.027), whereas gastrointestinal infection were found in 89 (8.4%) patients, who were more prone to develop AMAN (P=0.000), with more severe illness (P=0.001) and longer hospital stay (P=0.009). Children (≤15 years) and the elderly (≥56 years) were more severe at nadir, the elderly had the longest hospital stay (P=0.023). CONCLUSION: AIDP is the predominant form in southern China, which is different from data of northern China. The different subtypes, preceding infection and age of onset can partially determine the disease progression, severity and short-term recovery speed of GBS. CLINICAL TRIAL REGISTRATION: ChiCTR-RRC-17014152.

8.
Materials (Basel) ; 10(9)2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-28895926

RESUMO

The microstructural evolution and underlying mechanism of a new high strength, high toughness near ß titanium alloy, ß20C, during hot deformation, and heat treatment were studied qualitatively and quantitatively. It was found that dynamic recovery occurs mainly in ß phase, while α phase undergoes both a dynamic recovery and continuous incomplete dynamic recrystallization with a fraction of high-angle grain boundaries (≥15°) of 21.1% under hot-rolling. Subsequently, α phase undergoes static recrystallization with an increasing fraction of high-angle grain boundaries (21.1%→60.7%) under annealing, while the grains are equiaxed with refined grain sizes of 1.63 µm observed from the rolling direction (RD) and 1.66 µm observed from the transverse direction (TD). Moreover, the average aspect ratio of the lamellar α phase was 2.44 observed from the RD and 3.12 observed from the TD after hot rolling, but decreased to 2.20 observed from the RD, and 2.53 observed from the TD after annealing. Furthermore, the strict Burgers' relationship between α and ß phases changed after hot-rolling and remains the distortion, even after the static recrystallization process of α phase during annealing.

9.
J Med Chem ; 60(12): 5002-5014, 2017 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-28549219

RESUMO

Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.


Assuntos
Amidoidrolases/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Amidoidrolases/química , Animais , Antibacterianos/síntese química , Técnicas de Química Sintética , Cristalografia por Raios X , Desenho de Drogas , Avaliação Pré-Clínica de Medicamentos/métodos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Feminino , Células Hep G2/efeitos dos fármacos , Humanos , Células K562/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Relação Estrutura-Atividade
10.
Patient Prefer Adherence ; 10: 1071-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27366053

RESUMO

BACKGROUND: Cancer survivors with certain comorbidities had lower quality of life (QOL). This study was performed to investigate the prevalence of comorbidities and the association between comorbidities and the QOL among Chinese colorectal cancer survivors (CCS). METHODS: A cross-sectional study was conducted among 1,398 CCS between April and July 2013 in Shanghai, People's Republic of China. All the participants were asked to complete a simplified Chinese version of the European Organization for Research and Treatment quality of life version 3 questionnaire and questions on sociodemographic characteristics and comorbidities. In order to mitigate the bias caused by confounding factors, multiple linear regression models were employed to calculate the adjusted means of QOL scores. RESULTS: The proportion of participants without any comorbidity was only 20.2%. The CCS with comorbidities except hypertension scored significantly lower on the European Organization for Research and Treatment quality of life version 3 questionnaire global health and functioning scales and Functional Assessment of Cancer Therapy-General scales but higher on the European Organization for Research and Treatment quality of life version 3 questionnaire symptom scores, indicating that they had poorer QOL, particularly for cardiovascular, respiratory, digestive, and musculoskeletal diseases. CONCLUSION: There exists a significant association between comorbidities and QOL among Chinese CCS, and participants with comorbidities generally reported lower QOL scores. These findings suggested comprehensive care for CCS.

11.
J Med Chem ; 59(14): 6920-8, 2016 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-27355833

RESUMO

Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon- and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility.


Assuntos
Antibacterianos/farmacologia , Infecções por Clostridium/tratamento farmacológico , Clostridium difficile/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Tiazóis/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Cricetinae , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Solubilidade , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química
12.
BMC Public Health ; 15: 965, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26408314

RESUMO

BACKGROUND: Many gynecological cancer survivors (GCS) have comorbid chronic diseases (CCD). This study was to estimate the impacts of CCD on quality of life (QOL) in GCS. METHODS: We collected cross-sectional self-reported survey data from 598 GCS between April and July 2013, in Shanghai, China. All the subjects were asked to complete a questionnaire containing the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and questions on socio-demographic characteristics and CCD. In order to mitigate the bias caused by confounding factors, multiple linear models were employed to calculate adjusted means of QOL scores. RESULTS: Approximately three-quarters of subjects reported at least one CCD. The highest overall prevalence of all CCD was found in endometrial cancer survivors. Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 scales when compared to subjects without CCD, indicating poorer QOL, particularly for cardiovascular diseases, respiratory diseases, digestive diseases, and musculoskeletal disease. CONCLUSIONS: The CCD are common health problems among GCS. CCD have significantly negative influence on QOL, and GCS with CCD generally reported lower QOL scores. These findings suggested comprehensive cares for GCS.


Assuntos
Doença Crônica/psicologia , Neoplasias dos Genitais Femininos/psicologia , Qualidade de Vida , Sobreviventes , Adulto , Idoso , China/epidemiologia , Doença Crônica/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Neoplasias dos Genitais Femininos/epidemiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prevalência , Autorrelato
13.
Support Care Cancer ; 23(5): 1383-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25358644

RESUMO

PURPOSE: This study aimed to evaluate the influence of comorbid chronic diseases (CCD) and physical activity (PA) on quality of life (QOL) in lung cancer survivors (LCSs). METHODS: The study used a cross-sectional study design. A total of 701 LCSs were recruited from 17 comprehensive cancer rehabilitation clubs in Shanghai, China. Measurements used included the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy -General version 4 questionnaire (FACT-G). Independent variables were CCD and PA. Multiple linear regression models were used to control for the effect of sociodemographic characteristic. RESULTS: Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 and FACT-G scales when compared to subjects without CCD, indicating poorer QOL. Subjects with PA generally reported higher scores for most EORTC QLQ-C30 and FACT-G scales when compared to subjects without PA, indicating better QOL. The influences of five times and more PA per week were larger than the influence of less than five times PA per week. Subjects without CCD and with PA generally reported similar scores for most EORTC QLQ-C30 and FACT-G scales when compared to others without CCD and PA. Subjects with CCD and PA generally reported higher scores for most EORTC QLQ-C30 and FACT-G scales when compared to other LCSs with CCD and without PA. CONCLUSIONS: CCD have significantly negative influence on QOL. PA has significantly positive influence on QOL among the LCSs with CCD, not among the other LCSs without CCD.


Assuntos
Doença Crônica/psicologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/psicologia , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adulto , Idoso , China , Comorbidade , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Atividade Motora , Inquéritos e Questionários
14.
Chemistry ; 19(29): 9549-61, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23766090

RESUMO

The purposeful modulation of the optoelectronic properties was realised on the basis of a series of the large, conjugated, phosphine oxide hosts 9,9-bis-{4'-[2-(diphenylphosphinoyl)phenoxy]biphenyl-4-yl}-9H-fluorene (DDPESPOF), 9,9-bis-{3'-(diphenylphosphinoyl)-4'-[2-(diphenylphosphinoyl)phenoxy]biphenyl-4-yl}-9H-fluorene (DDPEPOF), 9-[4'-(9-{4'-[2-(diphenylphosphoryl)phenoxy]biphenyl-4-yl}-9H-fluoren-9-yl)biphenyl-4-yl]-9H-carbazole (DPESPOFPhCz) and 9-[4'-(9-{3'-(diphenylphosphoryl)-4'-[2-(diphenylphosphoryl)phenoxy]biphenyl-4-yl}-9H-fluoren-9-yl)biphenyl-4-yl]-9H-carbazole (DPEPOFPhCz). The last two are quaternary with fluorenyls as linking bridges, diphenylphosphine oxide (DPPO) moieties as electron acceptors and diphenylethers and carbazolyls as two different kinds of electron donors. Owing to the fine-organised molecular structures and the mixed indirect and multi-insulating linkages, all of these hosts achieve the same first triplet energy levels (T1) of 2.86 eV for exothermic energy transfer to phosphorescent dopants. The first singlet energy levels (S1) and the carrier injection/transportation ability of the hosts were accurately modulated, so that DPESPOFPhCz and DPEPOFPhCz revealed extremely similar optoelectronic properties. However, the T1 state of the former is localised on fluorenyl, whereas the carbazolyl mainly contributes to the T1 state of the latter. A lower driving voltages and much higher efficiencies of the devices based on DPESPOFPhCz indicated that the chromophore-localised T1 state can suppress the quenching effects through realising independent contributions from the different functional groups to the optoelectronic properties and the embedding and protecting effect on the T1 states by peripheral carrier transporting groups.

15.
Dalton Trans ; 42(22): 7888-93, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-23235504

RESUMO

The precise control of nanostructures, assembly processing, and the size of each component is important for the construction of integrated functional nanocomposites. In this paper, we describe a simple two-step method for the synthesis of novel flower-like nanocomposites (AuNPs/NiSiO) composed of well-dispersed and size-controlled Au nanoparticles (AuNPs) immobilized on hierarchically structured layered nickel silicate (NiSiO). The as-prepared AuNPs/NiSiO nanocomposites exhibited excellent catalytic activity in the reduction of 4-nitrophenol (4-NP). The experimental results proved that the size of AuNPs played an important role in enhancing the catalytic activity. In particular, there was no visible decrease in the catalytic activity of the reused catalysts even after being recycled five times. Therefore, the hierarchically nanostructured material can be a promising candidate as the catalytic support.


Assuntos
Ouro/química , Nanopartículas/química , Nanoestruturas/química , Níquel/química , Nitrofenóis/química , Silicatos/química , Catálise , Nanopartículas/ultraestrutura , Nanoestruturas/ultraestrutura , Oxirredução , Tamanho da Partícula
16.
Chem Asian J ; 7(12): 2955-61, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23042713

RESUMO

Layered nickel silicate nanoflowers (NSFs) with a hierarchical nanostructure have been successfully fabricated by a template-free solvothermal method. The as-prepared nanoflowers were composed of many interconnected edge-curving lamellae with a thickness of about 15 nm and had a high specific surface area (279 m(2) g(-1)) and large pore volume (0.67 cm(3) g(-1)). The highly dispersed small silver nanoparticles (AgNPs) were immobilized on the surface of NSFs through the in situ reduction of Ag(+) by Sn(2+). The AgNP/NSF nanocomposites showed a high performance in the catalytic reduction of 4-nitrophenol. In particular, there was no visible decrease in the catalytic activity of the reused catalysts even after being recycled four times. The as-prepared AgNP/NSF nanocomposites might be an excellent catalyst owing to their availability, formability, chemical and thermal stability, and high specific surface area.

17.
J Med Chem ; 55(15): 6934-41, 2012 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-22812377

RESUMO

Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) were initiated to improve chemical stability and physicochemical properties. Functional group modifications of 1 included removing the C2-C7 side chain, derivatizing the C84 epoxide region, and altering the C44 hydroxyphenylalanine motif. The resulting derivatives simplified and stabilized the chemical structure and were evaluated for antibacterial activity relative to 1. The simplified structure and improved organic solubility of the derivatives facilitated isolation yields from fermentation broths and simplified the procedures involved for the process. These advancements increased material supply for continued medicinal chemistry optimization and culminated in the identification of 2, a structurally simplified and chemically stable analogue of 1 which retained potent antibiotic activity.


Assuntos
Antibacterianos/síntese química , Peptídeos Cíclicos/síntese química , Tiazóis/síntese química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Clostridium difficile/efeitos dos fármacos , Cristalografia por Raios X , Enterococcus/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/biossíntese , Proteínas de Escherichia coli/química , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Fator Tu de Elongação de Peptídeos/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Inibidores da Síntese de Proteínas/síntese química , Inibidores da Síntese de Proteínas/química , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacologia , Transcrição Genética/efeitos dos fármacos
18.
Chem Commun (Camb) ; 48(49): 6157-9, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22590706

RESUMO

An ambipolar ternary deep-blue emitter with CIE coordinates of (0.15, 0.07) and high electroluminescent performance was constructed on the basis of an insulated donor-π-acceptor system through an indirect linkage.


Assuntos
Fluorenos/química , Medições Luminescentes/instrumentação , Óxidos/química , Fosfinas/química , Eletroquímica/instrumentação
19.
ACS Appl Mater Interfaces ; 4(5): 2781-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22548498

RESUMO

In this paper, TiO(2)/Ag sponge-like nanostructure composites have been prepared by the surface sol-gel method with the template of natural cellulose, which is relatively simple, low-cost, and environmentally friendly. The Ag nanoparticles are deposited on the TiO(2) nanosponges through UV irradiation photoreduction of silver nitrate solutions. The physicochemical properties of as-prepared composites are characterized by XRD, BET, SEM, TEM, XPS and UV-vis DRS techniques. The UV-light photocatalytic activities of the composites are evaluated through the photodegradation of two model organic molecules including RhB and salicylic acid. The experimental results show that the photocatalytic activities of TiO(2)/Ag nanosponge composites are superior to that of P25, pure TiO(2) nanoparticle aggregates synthesized by the hydrothermal method and pure TiO(2) nanosponge. The superior activities of TiO(2)/Ag nanosponge composite photocatalysts can be attributed to the unique nanosponge morphology, uniform dispersion of Ag nanoparticles, and strong interaction between Ag and TiO(2) nanosponges.

20.
J Med Chem ; 55(5): 2376-87, 2012 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-22315981

RESUMO

Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.


Assuntos
Antibacterianos/síntese química , Clostridium difficile/efeitos dos fármacos , Enterocolite Pseudomembranosa/tratamento farmacológico , Tiazóis/síntese química , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Cricetinae , Cristalografia por Raios X , Enterococcus/efeitos dos fármacos , Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas de Escherichia coli/química , Feminino , Masculino , Mesocricetus , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Fator Tu de Elongação de Peptídeos/antagonistas & inibidores , Fator Tu de Elongação de Peptídeos/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazóis/farmacocinética , Água
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