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1.
Org Lett ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792322

RESUMO

A copper-catalyzed one-pot perfluoroalkylation of alkynyl bromides and terminal alkynes has been disclosed, and the corresponding perfluoroalkylated alkynes could be attained in good to excellent yields. The new straightforward transformation shows high efficiency (0.01-0.5 mol % catalyst loading), broad substrate scope, and remarkable functional group tolerance and provides a facile approach for useful application in life and material sciences.

2.
Dalton Trans ; 50(9): 3369-3378, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33595584

RESUMO

The understanding of the correlation between the spin-state behaviour and the structural features in transition-metal complexes is of pronounced importance to the design of spin crossover compounds with high performance. However, the study of the influence of ligand symmetry on the spin crossover properties is still limited due to the shortage of suitable structural systems. Herein we report the magneto-structural correlations of three mononuclear Fe(ii) isomers with respect to their ligand symmetry. In this work, two phenyl-substituted meso and optically pure pybox ligands were employed to construct meso (1), optically pure (2), and racemic (3) ligand types of [Fe(pybox)2]2+ complexes. Their magnetic susceptibilities were measured via temperature-dependent paramagnetic 1H NMR spectroscopy. We fitted the midpoint temperatures of the transition (T1/2) of 260 K for 1(ClO4), 247 K for 2(ClO4), and 281 K for 3(ClO4). The influence of structural symmetry on spin crossover was rationalized through density functional theory calculations. The optimized structures of [Fe(pybox)2]2+ complex cations show that the geometric distortion of the central FeN6 coordination sphere is mainly caused by the steric congestions between adjacent phenyl substituents. In these compounds, there is a distinct correlation that more steric congestions produce larger coordination distortion and favor the electron configuration in the high-spin state, which reflects in the increase of T1/2. Additionally, the influence of the counter anion and lattice solvent on the meso series compounds was inspected. It is revealed that multiple factors dominate the spin-state behaviour in the solid state. This work provides deep insight into the effect of ligand symmetry on the spin transition behaviour in spin crossover compounds. It demonstrates that molecular symmetry should be considered in the design of spin crossover compounds.

3.
Phytomedicine ; 81: 153410, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33285470

RESUMO

BACKGROUND: Homocysteine (Hcy) induced vascular endothelial dysfunction is known to be closely associated with oxidative stress and impaired NO system. 1,8-Dihydroxy-3-methoxy-6-methylanthracene-9,10-dione (physcion) has been known to has antioxidative and anti-inflammatory properties. PURPOSE: The purpose of the present study was to define the protective effect of physcion on Hcy-induced endothelial dysfunction and its mechanisms involved. STUDY DESIGN AND METHODS: Hyperhomocysteinemia (HHcy) rat model was induced by feeding 3% methionine. A rat thoracic aortic ring model was used to investigate the effects of physcion on Hcy-induced impairment of endothelium-dependent relaxation. Two doses, low (L, 30 mg/kg/day) and high (H, 50 mg/kg/day) of physcion were used in the present study. To construct Hcy-injured human umbilical vein endothelial cells (HUVECs) model, the cells treated with 3 mM Hcy. The effects of physcion on Hcy-induced HUVECs cytotoxicity and apoptosis were studied using MTT and flow cytometry. Confocal analysis was used to determine the levels of intracellular Ca2+. The levels of protein expression of the apoptosis-related markers Bcl-2, Bax, caspase-9/3, and Akt and endothelial nitric oxide synthase (eNOS) were evaluated by western blot. RESULTS: In the HHcy rat model, plasma levels of Hcy and malondialdehyde (MDA) were elevated (20.45 ± 2.42 vs. 4.67 ± 1.94 µM, 9.42 ± 0.48 vs. 3.47 ± 0.59 nM, p < 0.001 for both), whereas superoxide dismutase (SOD) and nitric oxide (NO) levels were decreased (77.11 ± 4.78 vs. 115.02 ± 5.63 U/ml, 44.51 ± 4.45 vs. 64.18 ± 5.34 µM, p < 0.001 and p < 0.01, respectively). However, treatment with physcion significantly reversed these changes (11.82 ± 2.02 vs. 20.45 ± 2.42 µM, 5.97 ± 0.72 vs. 9.42 ± 0.48 nM, 108.75 ± 5.65 vs. 77.11 ± 4.78 U/ml, 58.14 ± 6.02 vs. 44.51 ± 4.45 µM, p < 0.01 for all). Physcion also prevented Hcy-induced impairment of endothelium-dependent relaxation in HHcy rats (1.56 ± 0.06 vs. 15.44 ± 2.53 nM EC50 for ACh vasorelaxation, p < 0.05 vs. HHcy). In Hcy-injured HUVECs, physcion inhibited the impaired viability, apoptosis and reactive oxygen species. Hcy treatment significantly increased the protein phosphorylation levels of p38 (2.26 ± 0.20 vs. 1.00 ± 0.12, p <0.01), ERK (2.11 ± 0.21 vs. 1.00 ± 0.11, p <0.01) and JNK. Moreover, physcion reversed the Hcy-induced apoptosis related parameter changes such as decreased mitochondrial membrane potential (MMP) and Bcl-2/Bax protein ratio, and increased protein expression of caspase-9/3 in HUVECs. Furthermore, the downregulation of Ca2+, Akt, eNOS and NO caused by Hcy were recovered with physcion treatment in HUVECs. CONCLUSION: Physcion prevents Hcy-induced endothelial dysfunction by activating Ca2+- and Akt-eNOS-NO signaling pathways. This study provides the first evidence that physcion might be a candidate agent for the prevention of cardiovascular disease induced by Hcy.

4.
Zhonghua Nan Ke Xue ; 26(8): 686-694, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33377728

RESUMO

Objective: To study the miR-184 level in the seminal plasma exosome of male infertility patients and its clinical significance. METHODS: Between 2015 and 2019, we collected 285 seminal plasma samples from 97 azoospermia (AS) and 96 asthenospermia (AZS) patients and 92 age-matched normal fertile controls in Jiangsu Provincial Hospital of Traditional Chinese Medicine, General Hospital of Eastern Theater Command and the First Hospital Affiliated to Wenzhou Medical University, identified the isolated seminal plasma exosomes by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot, and detected the miR-184 level in the seminal plasma exosomes by quantitative real-time PCR (qRT-PCR). We determined the clinical value of the miR-184 level and its correlation with semen parameters by multiple statistics, predicted the target genes and involved pathways of miR-184 by bioinformatic algorithms, and analyzed their relationship with male infertility. RESULTS: NTA, TEM and Western blot exhibited plenty of exosomes in the seminal plasma of the patients. The results of qRT-PCR showed that the miR-184 level in the seminal plasma exosome was dramatically decreased in the AS patients compared with that in the normal fertile controls (0.227 [0.092, 0.790] vs 0.650 [0.408, 1.061], P < 0.01), but increased in AZS males in comparison with that in the control group (1.176 [0.661, 1.946] vs 0.650 [0.408, 1.061], P < 0.01). The areas under the ROC curve (AUC) for differentiating the AS and AZS patients from the controls were 0.866 (95% CI: 0.815-0.916) and 0.724 (95% CI: 0.653-0.795), respectively, and that for differentiating the AS from the AZS group was 0.964 (95% CI: 0.943-0.985). The miR-184 level in the seminal plasma exosome of the AZS patients was correlated positively with the sperm count (r = 0.243, P = 0.017) but negatively with the percentage of progressively motile sperm (r = -0.407, P = 0.006). Bioinformatics analysis indicated that the downstream target genes of miR-184 were significantly enriched in the protein regulatory pathways closely related to male reproduction and spermatogenesis. CONCLUSIONS: The miR-184 level in the seminal plasma exosome of infertility patients is significantly different from that of normal fertile males, which may serve as a potential auxiliary marker for the diagnosis of and participate in the development and progression of male infertility.


Assuntos
Exossomos , Infertilidade Masculina , MicroRNAs/genética , Sêmen/química , Azoospermia , Estudos de Casos e Controles , Exossomos/genética , Humanos , Infertilidade Masculina/genética , Masculino , Contagem de Espermatozoides , Motilidade Espermática
5.
Curr Opin Pharmacol ; 54: 166-172, 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33176248

RESUMO

HIV-1 reverse transcriptase inhibitors (RTIs) are indispensable components of highly active antiretroviral therapy (HAART), which has achieved great success in controlling AIDS epidemic in reducing drastically the morbidity and mortality of HIV-infected patients. RTIs are divided into two categories, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). In this review, the recent discoveries in NRTIs and NNRTIs, including approved anti-HIV drugs and noteworthy drug candidates in different development stages, are summarized, and their future direction is prospected.

6.
Huan Jing Ke Xue ; 41(10): 4402-4412, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124372

RESUMO

To evaluate the effect of emergency emission reduction measures during the heavy air pollution episodes in Beijing, Tianjin, Hebei, and its surrounding areas, a scenario simulation method was used. The concentrations of PM2.5, PM10, SO2, NO2, CO, and O3-8h, air quality index (AQI), characteristics of heavy air pollution, and climate and meteorological factors were analyzed using the observation data available from October to December 2019. The 24 h, 72 h, and 144 h prediction results of NAQPMS model were analyzed. The uncertainties of the assessment and model prediction were discussed. The results showed that the average PM2.5 concentration in Beijing, Tianjin, and its surrounding 26 cities ("2+26" cities) from October to December 2019 was 64 µg ·m-3, indicating a decrease of 10 µg ·m-3 as compared with that during the same period in 2018. There were 4 occurrences of regional heavy air pollution episodes, with the average PM2.5 concentration of 156 µg ·m-3 of affected cities. The value of evaluation on meteorological condition index of PM2.5 pollution (EMI) of "2+26" cities ranged from -15.6%-16.8%. The meteorological conditions of 12 cities, including Beijing, Tianjin, and Shijiazhuang, deteriorated as compared with those during the same period in 2018, and the changes ranged from 3.2%-16.8%. However, the emergency emission reduction measures effectively reduced the occurrence of regional heavy air pollution episodes, the peak concentration of PM2.5 was decreased significantly, and no severe regional pollution episode occurred. The daily PM2.5 concentrations reduced by 2% to 9% in Beijing, Shijiazhuang, Baoding, Tangshan, and other cities during a typical heavy air pollution period. The quarterly average concentrations of PM2.5 in the "2+26" cities reduced by 1 to 3 µg ·m-3. The regional emergency emission reduction measures have played an active role in protecting the health of the people and improving the quality of ambient air.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Cidades , Monitoramento Ambiental , Humanos , Material Particulado/análise
7.
Huan Jing Ke Xue ; 41(2): 574-586, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608716

RESUMO

This study discusses the concentration characteristics of PM2.5 and PM10, as well as pollution meteorology in large-scale and long-term heavy pollution in the Beijing-Tianjin-Hebei region and its surrounding areas from November 23 to December 4, 2018, where the primary pollutants are comprised of PM2.5 and PM10. The monitoring results obtained from ground-based and vehicle-mounted lidars, as well as the HYSPLIT-4 backward trajectory combined with meteorological factors analysis are discussed. The accuracy and uncertainty of the air quality forecast model of NAQPMS, CMAQ, and CAMx during heavy air pollution were analyzed retrospectively. The results show that PM2.5 and sand dust in most cities in the south-central region contribute to severe pollution levels. The hourly peak concentrations of PM10 in Zhangjiakou, Beijing, Shijiazhuang, Handan, and Zhengzhou were 1589, 864, 794, 738, and 766 µg·m-3, respectively. The respective hourly peak concentrations of PM2.5 were 239, 319, 387, 321, and 380 µg·m-3. Ground static pressure field, high humidity, inversion, and other static and stable conditions, as well as sand dust transmitted from the northwest, were important pollution meteorological and weather factors. The monitoring data of ground-based lidar and vehicle-mounted lidar combined with the HYSPLIT-4 backward trajectory analysis showed that the air pollutant transmitted from the Southwest and Southeast during the heavy pollution period was primarily PM2.5. The air pollutant transmitted from the Northwest during the two sand dust processes. Moreover, the model of NAQPMS, CMAQ, and CAMx performed well in forecasting the heavy pollution process in the Beijing-Tianjin-Hebei region and its surrounding areas. However there are slight deviations for some individual cities, related to uncertainty in the meteorological model prediction, atmospheric chemical reaction mechanism, and pollution source list. Furthermore, the reduction in pollution source emissions caused by pollution emergency measures was also one of the main reasons for the overestimation.

8.
Childs Nerv Syst ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533299

RESUMO

PURPOSE: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems. The TSC1 and TSC2 genes have been identified as the genetic basis of TSC. Two gene tests were used for definitive genetic diagnosis. METHODS: In our study, the case of a Chinese pediatric patient with seizures, hypomelanotic macules, hyperpigmented patches, multiple parenchymal lesions in the ventricle, and developmental retardation is detailed. Whole-genome sequencing (WGS) and multiplex ligation-dependent probe amplification (MLPA) were employed to detect genetic variations and copy number variations of TSC1 and TSC2. RESULTS: A novel heterozygous nonsense mutation in the TSC2 gene (c.3751A>T, p.Lys1251Ter) was identified in a Chinese pediatric patient suffering from TSC, whose unaffected parents did not carry this mutation. The mutation was classified as "pathogenic" according to the American College of Medical Genetics (ACMG) guidelines. CONCLUSION: WGS was carried out to definitively diagnose and detect variations in the exon and noncoding region of the gene and copy number variations in the whole genome simultaneously. For diseases with complex genetic mechanisms, WGS as the first-line test can be efficient and cost-effective for clinical diagnosis.

9.
Inorg Chem ; 59(11): 7398-7407, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401025

RESUMO

The development of new spin-crossover complexes provides novel promising switching materials with significant potential at the molecular level. Ter-imine-type molecules represent one of the important classes of ligands in creating SCO-active complexes. Herein we report a family of mononuclear Fe(II) SCO-active compounds constructed from a new type of ter-imine ligand named the thio-pybox ligand (2,6-bis(4,4-dimethyl-4,5-dihydrothiazol-2-yl)pyridine, L1). Through the variation of counteranions, some cases display complete SCO and with T1/2 near ambient temperature. Among them, annealed [FeII(L1)2](ClO4)2 [1(ClO4)] shows T1/2↓ and T1/2↑ as 319 and 349 K, respectively. The wide thermal hysteresis of ΔT = 30 K originated from the weak interaction between complex cations and counteranions in the crystal lattice. Impressively, its high-spin population can be increased considerably by annealing at high temperature. The metastable high-spin phase is stable in the successive magnetic measurements and would gradually relax to its initial state with high population of low-spin configuration at ambient temperature. In acetonitrile-diluted solution, 1(ClO4) still maintains SCO with an estimated T1/2 at 240 K. Differential scanning calorimetry discloses the structural phase at around 355 K in the first heating process and the increase in the high-spin population concomitant with annealing was also corroborated by 57Fe Mössbauer measurements. Additionally, the influences on SCO by counteranion and ligand structure are investigated, which show that the fine tuning of complex structures can affect the behavior of the spin state significantly. Finally, magneto-structural correlation studies were performed on the structures of 1(ClO4) and its oxygen analogue at multiple temperatures. The analyses of some structural parameters, including terminal N···N donor separation, bite angle, patulous angle, and the root mean squared deviation indicate that the replacement of the oxygen atom with a sulfur atom can effectively improve the flexibility and release the steric strain and thus tune the SCO toward ambient temperature. Our research demonstrates the rational design of the ligand can lead to new SCO-active compounds with high performance.

10.
Eur J Med Chem ; 186: 111864, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31767136

RESUMO

A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with EC50 values ranging from 1.5 to 0.0064 µM. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC50 = 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC50 = 0.077 µM), Y181C (EC50 = 0.11 µM), E138K (EC50 = 0.057 µM), and moderate activity against double mutants RES056 (EC50 = 8.7 µM). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase.


Assuntos
Fármacos Anti-HIV/farmacologia , Desenho de Fármacos , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV/efeitos dos fármacos , Indazóis/farmacologia , Piperidinas/farmacologia , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Relação Dose-Resposta a Droga , Transcriptase Reversa do HIV/metabolismo , Humanos , Indazóis/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piperidinas/síntese química , Piperidinas/química , Pirimidinas/síntese química , Pirimidinas/química , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
11.
J Orthop Sci ; 25(4): 708-714, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31607516

RESUMO

BACKGROUND: The use of 3D-printed scaffolds in repairing bone defects remains unexplored. We aimed to determine whether the duration of electrochemical deposition (ECD) affects the properties of hydroxyapatite (HA) coatings on 3D-printed titanium (TI) scaffolds as well as the corresponding phenotype of MC3T3-E1 cells seeded on these surfaces. METHODS: Five groups of HA-coated TI scaffolds were produced using different durations of ECD (0, 5, 10, 20, and 30 min) and examined under scanning electron microscopy (SEM). MC3T3-E1 cell adhesion to the HA-coated scaffolds and subsequent proliferation and viability were assessed using SEM, DAPI staining, EdU staining, and Alamar Blue assay, respectively. MC3T3-E1 cell expression of osteogenic genes was analyzed by fluorescence RT-PCR. RESULTS: On SEM, longer ECD durations resulted in more compact HA crystals of differing morphology coated onto the TI scaffolds. MC3T3-E1 cell adhesion differed among the five groups (p < 0.05), with the largest number of cells adhered to the scaffolds prepared with 30 min of ECD, followed by the group prepared with 20 min of ECD. However, the ECD duration of 20 min was associated with the highest cell viability and proliferation rate (both p < 0.05) as well as the highest mRNA expression levels of alkaline phosphatase, collagen I, osteocalcin and runt-related transcription factor 2 among the five groups (p < 0.05). CONCLUSIONS: In the fabrication of HA-coated 3D printed TI scaffolds, an ECD duration of 20 min resulted in scaffolds that best promoted MC3T3-E1 cell viability, proliferation and osteogenic gene expression.

12.
Sci Prog ; 103(1): 36850419875662, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31829861

RESUMO

To improve the dynamic response performance of a high-flow electro-hydraulic servo system, scholars have conducted considerable research on the synchronous and time-sharing controls of multiple valves. However, most scholars have used offline optimization to improve control performance. Thus, control performance cannot be dynamically adjusted or optimized. To repeatedly optimize the performance of multiple valves online, this study proposes a method for connecting a high-flow proportional valve in parallel with a low-flow servo valve. Moreover, this study proposes an algorithm in which a proportional-integral-derivative system and multivariable predictive control system are used as an inner loop and outer loop, respectively. The simulation and experimental results revealed that dual-valve parallel control could effectively improve the control accuracy and dynamic response performance of an electro-hydraulic servo system and that the proportional-integral-derivative-multivariable predictive control controller could further dynamically improve the control accuracy.

13.
Huan Jing Ke Xue ; 40(12): 5191-5201, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854589

RESUMO

This paper discusses the concentration characteristics of PM2.5, as well as its relationship with meteorological factors in autumn and winter (from September to the following February), from 2013 to 2018 in the Beijing-Tianjin-Hebei (BTH) region. The accuracy and uncertainty of the air quality forecast models NAQPMS(nested air quality prediction modeling system), CMAQ(community multiscale air quality modeling system), and CAMx (comprehensive air quality model with extensions) were analyzed based on the model-predicted and measured PM2.5 concentration in autumn and winter from 2015 to 2018. The accuracy of NAQPMS, CMAQ, and CAMx during typical heavy air pollution was also tested. Moreover, methods to improve the accuracy of the model forecast were discussed. The results showed that the mean concentrations of PM2.5 in the BTH region were 122, 98, 82, 99, and 65 µg·m-3 in the five autumn and winter periods, respectively. When the air quality index (AQI) exceeded 150 during each autumn and winter, it reached 229, 198, 210, 204, and 180 µg·m-3, respectively. There were 64 occurrences of heavy regional PM2.5 air pollution in autumn and winter from 2013 to 2018. The average duration was longest in the 2013 to 2014 period, and shortest in the 2017 to 2018 period. The peak concentration and average concentration of PM2.5 decreased year on year, except for the period from 2016 to 2017. In autumn and winter, PM2.5 concentration had a relatively close relationship with relative humidity, wind and sunshine duration, compared with a weak relationship with temperature and air pressure. Regional heavy air pollution always happened under the condition of low wind speed(less than 2 m·s-1),higher relative humidity(greater than 65%),and southwest and northeast wind direction. In addition, the heavy air pollution of PM2.5 in BTH in autumn and winter can be effectively forecasted by NAQPMS, CMAQ, and CAMx. The predicted and measured PM2.5 concentration showed a close relationship. The models performed well in forecasting Zhangjiakou, Chengde, and Qinhuangdao, but by contrast overestimated in Tangshan, Shijiazhuang, Baoding, Beijing, and Tianjin. The uncertainty of emission sources, measured and predicted meteorological data, and the atmospheric chemical reaction mechanism may be the main reasons for the overestimate.

14.
Eur J Pharmacol ; 864: 172717, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586637

RESUMO

Homocysteine (Hcy) is an independent risk factor in the development of cardiovascular diseases (CVD). Hyperhomocysteinemia (HHcy), induces the injury of vascular endothelial cells via oxidative stress. Oxymatrine (OMT), one of the main components of Sophora flavescens, has displayed anti-inflammatory, anti-oxidant and anti-apoptotic activity. However, the effect of OMT on the Hcy-induced endothelial injury is not clearly defined yet. The aim of this study was to determine the protective effect of OMT on the Hcy-induced endothelial injury and its mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro. Methyl thiazolyl tetrazolium assay (MTT), fluorescence staining, flow cytometry and western blotting were used in this study. OMT prevented the Hcy-induced toxicity and apoptosis in HUVECs. Moreover, OMT suppressed Hcy-induced increases in reactive oxygen species, lactate dehydrogenase, malondialdehyde levels and increased superoxide dismutase levels. OMT reversed the Hcy-induced decrease in the protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2). In addition, OMT reversed the Hcy-induced apoptosis related biochemical changes such as decreased mitochondrial membrane potential and Bcl-2/Bax protein ratio, and increased protein expression of caspase-9 and caspase-3. Furthermore, OMT elevated the phosphorylation levels of Akt and eNOS, and the formation of nitric oxide (NO) in injured cells. These results suggest that OMT prevents Hcy-induced endothelial injury by regulating mitochondrial-dependent apoptosis and Akt-eNOS-NO signaling pathways concomitantly with accentuation of Nrf2 expression.


Assuntos
Alcaloides/farmacologia , Apoptose/efeitos dos fármacos , Homocisteína/efeitos adversos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolizinas/farmacologia , Citoproteção/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
15.
Eur J Neurosci ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31491043

RESUMO

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyse the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail.

16.
Eur J Med Chem ; 174: 277-291, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31051402

RESUMO

Since the entrance channel was proposed as a new binding site in non-nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) of HIV-1 reverse transcriptase (RT) in 2012, a huge number of HIV-1 inhibitors acting on this target have sprung up, aiming to discover promising inhibitors with excellent antiviral activities, physicochemical properties, and so on. From 2012 to 2018, many noteworthy compounds have been continuously discovered. In this review, the recent progress in HIV-1 inhibitors targeting the entrance channel of HIV-1 NNIBP was summarized and reviewed, which would provide useful clues and inspiration for further design of HIV-1 inhibitors.


Assuntos
Fármacos Anti-HIV/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Animais , Fármacos Anti-HIV/química , Sítios de Ligação , Linhagem Celular Tumoral , Transcriptase Reversa do HIV/química , Compostos Heterocíclicos/química , Humanos , Simulação de Acoplamento Molecular , Inibidores da Transcriptase Reversa/química
17.
Dalton Trans ; 48(19): 6323-6327, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30990479

RESUMO

Spin crossover and structural phase transition in three pairs of homochiral and heterochiral [Fe(pybox)2]2+ diastereomers were investigated through magnetic and crystallographic studies. Herein, we show that the spin transition properties of these compounds are strongly related to the homochiral or heterochiral assembly of the ligands and structural phase transition. Our work demonstrates that chirality is a feasible factor to modulate and influence the molecular geometry and thus the spin-crossover properties of complexes.

18.
Chemistry ; 25(33): 7866-7873, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30893491

RESUMO

A fluorophilic fluorescent probe based on a perfluoroalkyl-substituted bis(binaphthyl) compound was designed and synthesized. It displayed a highly enantioselective fluorescence response toward structurally diverse amino acids in a biphasic fluorous/aqueous system with enantiomeric fluorescent enhancement ratio (ef; ΔID /ΔIL ) values up to 45.2 (histidine). It can be used to determine the enantiomeric compositions of amino acids and also allows the amino acid enantiomers to be visually discriminated. NMR and mass-spectroscopic investigations provided insights into the observed high enantioselectivity. This biphasic fluorescent recognition was used to determine the enantiomeric composition of the crude phenylalanine products generated by an enzyme-catalyzed asymmetric hydrolysis under various reaction conditions. The fluorous-phase-based fluorescence measurement under the biphasic conditions was able to minimize the interference of other reaction components and thus has potential in asymmetric reaction screening.

19.
J Am Chem Soc ; 141(1): 175-181, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30525565

RESUMO

A novel fluorescent probe based on a bisbinaphthyl structure has been designed and synthesized. This compound in combination with Zn(II) has exhibited highly enantioselective fluorescence enhancement with 13 common free amino acids. For example, its enantiomeric fluorescent enhancement ratios ( ef or Δ IL/Δ ID) in the presence of the following amino acids are extremely high: 177 for valine, 199 for methionine, 186 for phenylalanine, 118 for leucine, and 89 for alanine. The observed high enantioselectivity and the extent of the substrate scope are unprecedented in the fluorescent recognition of free amino acids. This fluorescent probe can be applied to determine the enantiomeric composition of the structurally diverse chiral amino acids. NMR and mass spectroscopic investigations have provided clues to elucidate the observed high enantioselectivity.

20.
Eur J Med Chem ; 158: 371-392, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30223123

RESUMO

HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been playing an important role in the fight against acquired immunodeficiency syndrome (AIDS). Diarylpyrimidines (DAPYs) as the second generation NNRTIs, represented by etravirine (TMC125) and rilpivirine (TMC278), have attracted extensive attention due to their extraordinary potency, high specificity and low toxicity. However, the rapid emergence of drug-resistant virus strains and dissatisfactory pharmacokinetics of DAPYs present new challenges. In the past two decades, an increasing number of novel DAPY derivatives have emerged, which significantly enriched the structure-activity relationship of DAPYs. Studies of crystallography and molecular modeling have afforded a lot of useful information on structural requirements of NNRTIs, which contributes greatly to the improvement of their resistance profiles. In this review, we reviewed the discovery history and their evolution of DAPYs including their structural modification, derivatization and scaffold hopping in continuous pursuit of excellent anti-HIV drugs. And also, we discussed the prospect of DAPYs and the directions of future efforts.


Assuntos
Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/enzimologia , Pirimidinas/química , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Transcriptase Reversa do HIV/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
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