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1.
J Am Chem Soc ; 146(8): 5643-5649, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38327018

RESUMO

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

2.
Mar Environ Res ; 195: 106378, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266549

RESUMO

The increasing prevalence of phosphorus limitation in coastal waters has drawn attention to the bioavailability of cellular surface-adsorbed phosphorus (SP) as a reservoir of phosphorus in phytoplankton. This study examined the storage, utilization, and regulation of SP in the coastal waters of the East China Sea, as well as three cultivated algal bloom species (Skeletonema marinoi, Prorocentrum shikokuense, and Karenia mikimotoi) prevalent in the area. SP accounted for 14.3%-45.5% of particulate phosphorus in the field and laboratory species. After the depletion of external phosphate, the studied species can rapidly transport SP within 3-24 h. The storage of SP is regulated by both external phosphate conditions and the internal growth stage of cells, but it is not influenced by the various cellular surface structures of the studied species. This study highlights the significance of SP as a crucial phosphorus reservoir and the potential use of the SP level as an indicator of phosphorus deficiency in phytoplankton.


Assuntos
Dinoflagellida , Microalgas , Fosfatos , Fitoplâncton/fisiologia , Fósforo , China , Proliferação Nociva de Algas
3.
Org Lett ; 26(1): 89-93, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38127266

RESUMO

Different from electronically matched 1,4- and 1,6-additions, herein, we disclose an electronically mismatched 1,5-conjugate addition process with oximes as the nucleophiles. By this design, the oxime moieties are readily introduced to the γ-position of the electron-deficient substrates in good yields, excellent regioselectivities, and high enantioselectivities. The corresponding allyl oximes are also conveniently transformed into a series of valuable enantioenriched skeletons.

4.
J Biol Chem ; 299(11): 105335, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37827291

RESUMO

Hepatoma-derived growth factor (HDGF) overexpression and uncontrolled reactive oxygen species (ROS) accumulation are involved in malignant transformation and poor prognosis in various types of cancer. However, the interplay between HDGF and ROS generation has not been elucidated in hepatocellular carcinoma. Here, we first analyzed the profile of HDGF expression and ROS production in newly generated orthotopic hepatomas by ultrasound-guided implantation. In situ superoxide detection showed that HDGF-overexpressing hepatomas had significantly elevated ROS levels compared with adjacent nontumor tissues. Consistently, liver tissues from HDGF-deficient mice exhibited lower ROS fluorescence than those from age- and sex-matched WT mice. ROS-detecting fluorescent dyes and flow cytometry revealed that recombinant HDGF (rHDGF) stimulated the production of superoxide anion, hydrogen peroxide, and mitochondrial ROS generation in cultured hepatoma cells in a dose-dependent manner. In contrast, the inactive Ser103Ala rHDGF mutant failed to promote ROS generation or oncogenic behaviors. Seahorse metabolic flux assays revealed that rHDGF dose dependently upregulated bioenergetics through enhanced basal and total oxygen consumption rate, extracellular acidification rate, and oxidative phosphorylation in hepatoma cells. Moreover, antioxidants of N-acetyl cysteine and MitoQ treatment significantly inhibited HDGF-mediated cell proliferation and invasive capacity. Genetic silencing of superoxide dismutase 2 augmented the HDGF-induced ROS generation and oncogenic behaviors of hepatoma cells. Finally, genetic knockdown nucleolin (NCL) and antibody neutralization of surface NCL, the HDGF receptor, abolished the HDGF-induced increase in ROS and mitochondrial energetics. In conclusion, this study has demonstrated for the first time that the HDGF/NCL signaling axis induces ROS generation by elevating ROS generation in mitochondria, thereby stimulating liver carcinogenesis.


Assuntos
Carcinoma Hepatocelular , Animais , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Espécies Reativas de Oxigênio , Carcinogênese/genética
5.
Angew Chem Int Ed Engl ; 62(15): e202300691, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36786065

RESUMO

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pKa Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

6.
J Am Chem Soc ; 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36763785

RESUMO

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit in synthetic chemistry. Abundant applications of free enantioenriched allyl alcohol and allyl hydroxylamine motifs have made the asymmetric hydration and hydroaminoxylation of conjugated dienes from water and hydroxylamine, respectively, intriguing and efficient routes that have, however, been unachievable thus far. A fundamental challenge is the failure to realize transition-metal-catalyzed enantioselective C-O bond constructions via hydrofunctionalization of conjugated dienes. Here, we perform a comprehensive study toward the stereoselective formal hydration and hydroaminoxylation of conjugated dienes by synthesizing a set of new P,N-ligands and identifying an aryl-derived oxime as a surrogate for both water and hydroxylamine. Asymmetric hydroalkoxylation with new P,N-ligands is also elucidated. Furthermore, versatile derivatizations following hydration provide indirect but concise routes to formal hydrophenoxylation, hydrofluoroalkoxylation, and hydrocarboxylation of conjugated dienes that have been unreported thus far. Finally, a ligand-to-ligand hydrogen transfer process is proposed based on the results of preliminary mechanistic experiments.

7.
Molecules ; 25(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066044

RESUMO

Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound (A14), with a docking score of -10.6 kcal⋅mol-1, was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.


Assuntos
Benzofuranos/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Lipase/química , Benzofuranos/farmacologia , Domínio Catalítico , Humanos , Ligação de Hidrogênio , Ligantes , Lipase/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Orlistate/química
8.
Ecotoxicol Environ Saf ; 205: 111350, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961487

RESUMO

Atmospheric nitrogen dioxide (NO2) negatively affects plant (crop) growth and development, as well the yield and quality in some regions or environments. Arbuscular mycorrhizal fungus (AMF)-mediated amelioration of NO2-induced plant damage has been reported, but the underlying mechanisms remained unclear. This study explored the beneficial effect of AMF symbiosis on tomato plant responses to NO2 at physiology, biochemistry, and gene expression, with an emphasis on nitrate metabolism, antioxidative defense, and photosynthetic performance. Pot-grown plants were used in the experiments, which were performed in laboratory from February to November 2019. NO2 fumigation with a dose of 10 ± 1 ppm was carried out after 50 d of plant growth, and data were collected following 8 h of fumigation. NO2 fumigation (+NO2) and AMF inoculation (+AMF), alone and especially in combination (NO2 + AMF), increased the gene expression of nitrate- and nitrite reductase, and their enzymatic activity in leaves, such as by 61%, 27%, and 126% for the activity of nitrate reductase, and by 95%, 37%, and 188% for nitrite reductase, respectively, in +NO2, +AMF, and AMF + NO2 plants relative the control (-NO2, -AMF) levels. Following NO2 exposure, +AMF leaves displayed stronger activities of superoxide dismutase, peroxidase and catalase, and higher content of glutathione and ratio of its reduced form to oxidized form, as compared with -AMF ones. Correspondingly, lesser oxidative damage was detected in +AMF than in -AMF plants, as indicated by the contents of H2O2 and malondialdehyde, electrolyte leakage, also by in situ visualization for the formation of H2O2, superoxide anion, and dead cells. The increased antioxidative capacity in +AMF plants was correlated with enhanced expression of antioxidation-related genes. Exposure to NO2 substantially impaired photosynthetic processes in both + AMF and -AMF plants, but an obvious mitigation was observed in the former than in the latter. For example, the total chlorophyll, net photosynthetic rate, stomatal conductance, and ribulose-1,5-bisphosphate carboxylase activity were 18%, 27%, 26%, and 40% higher, respectively, in +AMF than in -AMF plants under NO2 stress. The differential photosynthetic performance was also revealed by chlorophyll fluorescence imaging. We analyzed the expression patterns of some genes related to photosynthesis and carbon metabolisms, and found that all of them exclusively presented a higher expression level in +AMF plants relative to -AMF ones under NO2 stress. Taken together, this study provided evidence that AMF symbiosis played a positively regulatory role in host plant responses to NO2, probably by increasing leaf nitrate metabolism and antioxidative defense, and maintaining the photosynthetic efficiency to some extent, wherein the transcription regulation might be a main target.


Assuntos
Micorrizas/fisiologia , Dióxido de Nitrogênio/toxicidade , Solanum lycopersicum/fisiologia , Antioxidantes/metabolismo , Clorofila/metabolismo , Peróxido de Hidrogênio/metabolismo , Solanum lycopersicum/metabolismo , Solanum lycopersicum/microbiologia , Micorrizas/metabolismo , Oxirredução , Fotossíntese/fisiologia , Desenvolvimento Vegetal , Folhas de Planta/metabolismo
9.
Journal of Medical Postgraduates ; (12): 791-796, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-818325

RESUMO

Objective N-acety-L-cysteine (NAC) can attenuate the injury of podocytes and renal tubular epithelial HK-2 cells induced by contrast agents, but its specific action mechanisms needs to be further clarified. In this study, we investigated the effects of NAC on iopromide (IPM)-induced injury and the NF-κB/NLRP3 signaling pathway in HK-2 cells. Methods Renal tubular epithelial HK-2 cells were divided into seven groups, control, IPM, and IPM + NAC at 2, 4, 8, 16 and 32 mmol/L. After a 24-hour treatment of the HK-2 cells with NAC, CCK-8, DAPI staining, DCFH-DA and Western blot were employed for determination of the viability, apoptosis and morphology of the cells as well as the level of reactive oxygen species (ROS) and the expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB in the cells. Results Compared with the control, the cells of the IPM group showed a significantly reduced viability ([100 ± 4.749]% vs [48.819 ± 2.045]%, P < 0.05), increased apoptosis, elevated ROS level, and up-regulated expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB. In comparison with the IPM group, the HK-2 cells treated with NAC at 2, 4, 8, 16 and 32 mmol/L exhibited a remarkably increased viability ([55.398 ± 3.609]%, [58.953 ± 2.859]%, [61.531 ± 5.179]%, [59.845 ± 6.365]% and [59.094 ± 6.285]%) and decreased ROS level and expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB. The mean fluorescence intensity was significantly higher in the HK-2 cells of the IPM group than in the control cells (5050.85 ± 606.76 vs 1502.17 ± 55.91, P < 0.05), but remarkably decreased in those treated with NAC at 2, 4, 8, 16 and 32 mmol/L (4065.39 ± 106.59, 4162.05 ± 28.93, 3675.71 ± 50.38, 3133.79 ± 66.07 and 2675.80 ± 92.39) (P < 0.05). Conclusion NAC can effectively improve IPM-induced injury of renal tubular epithelial cells, which may be associated with its abilities of inhibiting ROS production and activating the NF-κB/NLRP3 signaling pathway.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(9): 729-733, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30210024

RESUMO

OBJECTIVE: To compare the efficacy between synchronized intermittent mandatory ventilation (SIMV) and pressure support ventilation with volume guarantee (PSV+VG) in the weaning phase of preterm infants with respiratory distress syndrome (RDS). METHODS: Forty preterm infants with RDS who were admitted to the neonatal intensive care unit between March 2016 and May 2017 were enrolled as subjects. All infants were born at less than 32 weeks' gestation and received mechanical ventilation. These patients were randomly and equally divided into SIMV group and PSV+VG group in the weaning phase. Ventilator parameters, arterial blood gas, weaning duration (from onset of weaning to extubation), duration of nasal continuous positive airway pressure (NCPAP) after extubation, extubation failure rate, the incidence rates of pneumothorax, patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD), and the mortality rate were compared between the two groups. RESULTS: The PSV+VG group had significantly decreased mean airway pressure, weaning duration, duration of NCPAP after extubation, and extubation failure rate compared with the SIMV group (P<0.05). There were no significant differences in arterial blood gas, mortality, or incidence rates of pneumothorax, PDA and BPD between the two groups (P>0.05). CONCLUSIONS: For preterm infants with RDS, the PSV+VG mode may be a relatively safe and effective mode in the weaning phase. However, multi-center clinical trials with large sample sizes are needed to confirm the conclusion.


Assuntos
Síndrome do Desconforto Respiratório do Recém-Nascido , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Ventilação com Pressão Positiva Intermitente , Desmame do Respirador
11.
Toxicol Ind Health ; 34(4): 253-261, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29514563

RESUMO

The present study combined air sampling with pulmonary function tests (PFTs) to determine both the extent of air pollution proximal to an electric arc furnace (EAF) and its impact on human health. The mass concentrations of particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) in exposure areas were not significantly higher than the samples taken at a control area. However, the concentrations of five metal elements, Cd, Cr, Cu, Ni, and Zn in PM2.5 were significantly higher in the exposure area than that of the control area. PFTs showed that the average forced vital capacity (FVC) of boys was decreased with decreasing distance from the EAF factory. With normalization of pulmonary function by age, height, and weight, we found that the FVC became more negative with a decrease in distance from the EAF. Lastly, regression analysis was performed to analyze the impact of the concentrations of the five metals in PM2.5 on the performance of pulmonary function. The results showed that the metals can be ranked from the highest to the lowest in terms of impact on the FVC of boys as follows: Cr, Cd, Ni, Cu, and Zn. This finding is consistent with the ranking of metal toxicity reported in the literature for a rat lung epithelial cell line. The results of this study showed that only measuring PM2.5 mass concentrations may not provide a full explanation of its toxicity and health effects. The chemical composition of the PM2.5 can be an important factor that determined the health impact of PM2.5.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Calefação/efeitos adversos , Metais/toxicidade , Material Particulado/toxicidade , Adolescente , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cádmio/análise , Cádmio/toxicidade , Criança , Cromo/análise , Cromo/toxicidade , Cobre/análise , Cobre/toxicidade , Monitoramento Ambiental , Calefação/métodos , Humanos , Metais/análise , Níquel/análise , Níquel/toxicidade , Material Particulado/análise , Regressão Psicológica , Testes de Função Respiratória , Instituições Acadêmicas , Taiwan , Zinco/análise , Zinco/toxicidade
12.
Int J Ophthalmol ; 10(4): 507-514, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28503420

RESUMO

AIM: To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial (RPE) cells. METHODS: Human RPE cell lines (ARPE-19 cell) were treated with different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2). Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay. EGFR/AKT signaling was detected by Western blot. EGFR localization was also detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK-2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine (NAC). RESULTS: EGF treatment increased ARPE-19 cell viability and proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through alleviating reduction of EGFR, and phosphorylated and total AKT proteins. CONCLUSION: Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway. The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.

13.
Pharmacology ; 100(1-2): 91-97, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28494448

RESUMO

AIMS: CYP2C19 is an important member of the cytochrome P450 enzyme superfamily. We recently identified 31 CYP2C19 alleles in the Han Chinese population. The aim of this study was to assess the catalytic activities of these allelic isoforms and their effects on the metabolism of fluoxetine in vitro. METHODS: The wild-type and 30 CYP2C19 variants were expressed in insect cells and each variant was characterized using fluoxetine as the substrate. Reactions were performed at 37°C with 20-1,000 µmol/L substrate for 30 min. By using ultra-high performance liquid chromatography-mass spectrometry to detect the products, the kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of norfluoxetine were determined. RESULTS: Among the CYP2C19 variants tested, T130M showed similar intrinsic clearance (Vmax/Km) values with CYP2C19*1, while the intrinsic clearance values of other variants were significantly decreased (from 9.56 to 77.77%). In addition, CYP2C19*3 and *35FS could not be detected because they have no detectable enzyme activity. CONCLUSION: In China, the assessment of CYP2C19 variants in vitro offers valuable information relevant to the personalized medicine for CYP2C19-metabolized drug.


Assuntos
Citocromo P-450 CYP2C19/genética , Fluoxetina/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Alelos , Animais , Povo Asiático/genética , Cromatografia Líquida de Alta Pressão , Fluoxetina/análogos & derivados , Variação Genética , Humanos , Espectrometria de Massas , Células Sf9
14.
Int J Clin Exp Med ; 8(8): 14184-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26550393

RESUMO

The ischemia necrosis of limb frequently requires surgery of amputation. Lumbar plexus and sciatic nerve block is an ideal intra-operative anesthetic and post-operative antalgic technique for patients of amputation, especially for high-risk patients who have severe cardio-cerebrovascular diseases. However, the duration of analgesia of peripheral nerve block is hardly sufficient to avoid the postoperative pain and the usage of opioids. In this case, a 79-year-old man, with multiple cerebral infarcts, congestive heart failure, atrial flutter and syncope, was treated with an above knee amputation because of ischemia necrosis of his left lower limb. Dexmedetomidine 1 µg/kg was added to 0.33% ropivacaine for lumbar plexus and sciatic nerve block in this case for intra-operative anesthesia and post-operative analgesia. The sensory function was blocked fully for surgery and the duration of analgesia maintained 26 hours with haemodynamic stability and moderate sedation. The patient did not complain pain and require any supplementary analgesics after surgery. This case showed that adding 1 µg/kg dexmedetomidine to ropivacaine for lumbar plexus and sciatic nerve block may be a feasible and safe technique for high-risk patients for lower limb surgery of amputation.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(3): 281-6, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-25815501

RESUMO

OBJECTIVE: To examine the expression of calreticulin (CRT) and the changes of intracellular free calcium and neuronal apoptosis in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage (HIBD), and to investigate the intervention effects of Shenfu injection. METHODS: Seven-day-old rats were randomly assigned to three groups: control, hypoxic-ischemia (HI) and Shenfu-treated. Each group (n=50) was subdivided into 5 groups sacrificed at 3, 6, 12, 24 and 72 hours. Rat models of HIBD were prepared according to the Rice's method. Rats in the control group only underwent the separation of right common carotidartery. Shenfu injection was administered by intraperitoneal injections right after HI insults and then once daily at a dosage of 10 mL/kg for 3 days in the Shenfu-treated group. The expression of CRT in the cerebral cortex was detected by RT-PCR and Western blot. The free calcium concentrations were determined under a fluorescent microscope. The apoptosis rate was measured by the flow cytometry. RESULTS: Compared with the control group, the expression levels of CRT in the HI and the Shenfu-treated groups were obviously up-regulated (P<0.05), and the expression levels of CRT in the Shenfu-treated group were notably higher than those in the HI group (P<0.05) at all time points. The concentrations of intracellular free calcium and the apoptosis rate of neurons in the cerebral cortex in the Shenfu-treated group were significantly reduced compared with those in the HI group (P<0.05), but increased significantly compared with those in the control group at all time points (P<0.05). CONCLUSIONS: Shenfu injection may have neuroprotective effects against HIBD by up-regulation of CRT expression and relief of calcium overload.


Assuntos
Apoptose/efeitos dos fármacos , Calreticulina/análise , Córtex Cerebral/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Neurônios/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Córtex Cerebral/patologia , Feminino , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Injeções , Masculino , Ratos Sprague-Dawley
16.
Magn Reson Chem ; 52(6): 306-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24700676

RESUMO

Two new indole-diterpenoids 4b-deoxy-1'-O-acetylpaxilline (1) and 4b-deoxypenijanthine A (2) were isolated from the fermentation broth and the mycelia of the soil fungus Penicillium sp. CM-7, along with three known structurally related compounds, 1'-O-acetylpaxilline (3), paspaline (4) and 3-deoxo-4b-deoxypaxilline (5). The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods, especially 2D NMR, and their absolute configurations were suggested on the basis of the circular dichroism spectral analysis and the NOESY data.


Assuntos
Diterpenos/química , Indóis/química , Espectroscopia de Ressonância Magnética/métodos , Penicillium/classificação , Penicillium/metabolismo , Diterpenos/análise , Indóis/análise , Conformação Molecular , Especificidade da Espécie
17.
J Exp Bot ; 65(1): 223-34, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24187420

RESUMO

Production per amount of water used (water use efficiency, WUE) is closely correlated with drought tolerance. Although stomatal aperture can regulate WUE, the underlying molecular mechanisms are still unclear. Previous reports revealed that stomatal closure was inhibited in the calcium-sensing receptor (CAS) antisense line of Arabidopsis (CASas). Here it is shown that decreased drought tolerance and WUE of CASas was associated with higher stomatal conductance due to improper regulation of stomatal aperture, rather than any change of stomatal density. CASas plants also had a lower CO2 assimilation rate that was attributed to a lower photosynthetic electron transport rate, leading to higher chlorophyll fluorescence. Gene co-expression combined with analyses of chlorophyll content and transcription levels of photosynthesis-related genes indicate that CAS is involved in the formation of the photosynthetic electron transport system. These data suggest that CAS regulates transpiration and optimizes photosynthesis by playing important roles in stomatal movement and formation of photosynthetic electron transport, thereby regulating WUE and drought tolerance.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Ligação ao Cálcio/genética , Cálcio/metabolismo , Regulação da Expressão Gênica de Plantas , Água/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Desidratação , Secas , Transporte de Elétrons , Modelos Biológicos , Fotossíntese/fisiologia , Epiderme Vegetal/genética , Epiderme Vegetal/fisiologia , Folhas de Planta/genética , Folhas de Planta/fisiologia , Estômatos de Plantas/genética , Estômatos de Plantas/fisiologia , Transpiração Vegetal/fisiologia , Fatores de Tempo
18.
Biochem J ; 456(1): 35-46, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23992409

RESUMO

Previous studies have demonstrated that both retinoids and apelin possess potent cardiovascular properties and that retinoids can mediate the expression of many genes in the cardiovascular system. However, it is not clear whether and how retinoids regulate apelin expression in rat VSMCs (vascular smooth muscle cells). In the present study, we investigated the molecular mechanism of apelin expression regulation by the synthetic retinoid Am80 in VSMCs. The results showed that Am80 markedly up-regulated apelin mRNA and protein levels in VSMCs. Furthermore, KLF5 (Krüppel-like factor 5) and Sp1 (stimulating protein-1) co-operatively mediated Am80-induced apelin expression through their direct binding to the TCE (transforming growth factor-ß control element) on the apelin promoter. Interestingly, upon Am80 stimulation, the RARα (retinoic acid receptor α) was recruited to the apelin promoter by interacting with KLF5 and Sp1 prebound to the TCE site of the apelin promoter to form a transcriptional activation complex, subsequently leading to the up-regulation of apelin expression in VSMCs. An in vivo study indicated that Am80 increased apelin expression in balloon-injured arteries of rats, consistent with the results from the cultured VSMCs. Thus the results of the present study describe a novel mechanism of apelin regulation by Am80 and further expand the network of RARα in the retinoid pathway.


Assuntos
Benzoatos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Fatores de Transcrição Kruppel-Like/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Receptores do Ácido Retinoico/metabolismo , Fator de Transcrição Sp1/metabolismo , Tetra-Hidronaftalenos/farmacologia , Animais , Apelina , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley , Receptores do Ácido Retinoico/agonistas , Receptor alfa de Ácido Retinoico , Transdução de Sinais , Transcrição Gênica , Fator de Crescimento Transformador beta/genética , Regulação para Cima , Dedos de Zinco
19.
FEBS Lett ; 587(9): 1326-32, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23499936

RESUMO

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in atherosclerosis and restenosis. In this paper, we report that Y-box binding protein 1 (YB1) functions as a phenotypic regulator in VSMC proliferation-differentiation switching through targeting GC box-dependent genes. Oligo pull-down assays demonstrated that YB1 binds directly to GC boxes via amino acids 125-220. YB1 C-terminal tail domain (CTD, amino acids 125-324) regulates GC box-dependent target gene transcription and suppresses VSMC proliferation. These findings provide a novel insight into the regulation of GC box-related genes by YB1, and provide a new understanding of VSMC proliferation regulation.


Assuntos
Músculo Liso Vascular/citologia , Motivos de Nucleotídeos/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Animais , Sequência de Bases , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Motivos de Nucleotídeos/efeitos dos fármacos , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , Fenótipo , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Tretinoína/farmacologia , Proteína 1 de Ligação a Y-Box/química
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(10): 2651-4, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24409710

RESUMO

The impact of the high-temperature phase change material on conventional infrared decoy's combustion performance and infrared radiation characteristics was studied. The selected high-temperature phase change materials did not reduce infrared radiation in the 3-5 microm or 8-14 microm band of infrared decoy, while extended the burning time, and reduced the burning rate of the grain, thus prolonged the effective interference time of IR decoy. The results show the phase change material is effective infrared decoy functional additives.

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