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1.
Bioorg Chem ; 135: 106491, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37011521

RESUMO

PTP1B plays an important role as a key negative regulator of tyrosine phosphorylation associated with insulin receptor signaling in the therapy for diabetes and obesity. In this study, the anti-diabetic activity of dianthrone derivatives from Polygonum multiflorum Thunb., as well as the structure-activity relationships, mechanism, and molecular docking were explored. Among these analogs, trans-emodin dianthrone (compound 1) enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice. By using photoaffinity labeling and mass spectrometry-based proteomics, we discovered that trans-emodin dianthrone (compound 1) may bind to PTP1B allosteric pocket at helix α6/α7, which provides fresh insight into the identification of novel anti-diabetic agents.


Assuntos
Diabetes Mellitus , Emodina , Fallopia multiflora , Camundongos , Animais , Fallopia multiflora/química , Fallopia multiflora/metabolismo , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
2.
BMC Nephrol ; 24(1): 238, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582785

RESUMO

BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS: Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.


Assuntos
Doença da Artéria Coronariana , Calcificação Vascular , Humanos , Diálise Renal/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Hormônio Paratireóideo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/etiologia , Peptídeos , Fosfatase Alcalina
3.
Inorg Chem ; 61(30): 11775-11786, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35858285

RESUMO

Sulfur oxides from the combustion of petrol and excessive emissions of carbon dioxide (CO2) are currently the main causes of environmental pollution. Considerable interest has been paid to solving the challenge, and catalytic reactions seem to be the desired choice. Due to the high density of Lewis acid active sites, polyoxometalates are considered to be the ideal choice for these catalytic reactions. Herein, two captivating polyoxometalate-based metal-organic complexes, formulated as [Co(H2O)2DABT]2[CrMo6(OH)5O19] ({Co-CrMo6}) and [Zn(H2O)2DABT]2[CrMo6(OH)5O19] ({Zn-CrMo6}) (DABT = 3,3'-diamino-5,5'-bis(1H-1,2,4-triazole)) were successfully obtained under hydrothermal conditions. The structural analysis demonstrates that {Co-CrMo6} and {Zn-CrMo6} are isostructural with two different transition metal (Co/Zn) ions based on quadridentate Anderson-type [CrMo6(OH)5O19]4- polyanions. A fan-shaped unit of {Co-CrMo6}/{Zn-CrMo6} is linked to generate a one-dimensional (1D) ladder-like structure. Intriguingly, benefitting from rich Co centers with a suitable energy band structure, {Co-CrMo6} displays better photocatalytic activity than {Zn-CrMo6} for converting CO2 into CO, endowing the CO formation of 1935.3 µmol g-1 h-1 with high selectivity. Meanwhile, {Co-CrMo6} also exhibits a satisfactory removal rate of 99% for oxidizing dibenzothiophene at 50 °C, which suggests that {Co-CrMo6} may be utilized as a potential dual functional material with immense prospects in photocatalytic CO2 reduction and sulfur oxidation for the first time.

4.
Inorg Chem ; 61(50): 20397-20404, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36459670

RESUMO

Hydrogen energy is a renewable and clean source, which makes a great difference in future sustainable energy systems. Visible-light-driven photocatalysis reaction involves harnessing the abundance of sunlight for hydrogen production among many catalytic technologies. However, the fabrication of photocatalysts that have distinctive performance in visible light is still the primary challenge. Herein, two new Cu-modified polyoxotungstate hybrids, {[Cu2(bim)4(H2O)2](HBW12O40)2·(H2bim)2·8H2O} (1) (bim = [1,1'-methylenebis(1H-imidazole)]) and {[Cu2(bim)4(H2O)2](H3PW10Ti2O40)2·(H2bim)2·8H2O} (2), have been successfully isolated by bridging two saturated Keggin polyoxotungstates and copper-azole complexes. Not surprisingly, 2 holds higher reduction activity due to the more negative charge and stronger basicity on the terminal oxygen of Ti═O and bridge oxygen of Ti-O-W. The H2 yield was 17075 µmol g-1 h-1 for 2 in the tunable light-driven H2 production system, which is promising in the field of photocatalysis.

5.
Molecules ; 27(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35807284

RESUMO

Cephalanthus tetrandrus (Roxb.) Ridsd. et Badh. F. (CT) belongs to the Rubiaceae family. Its dried leaves are widely used in traditional Chinese medicine to treat enteritis, dysentery, toothache, furuncles, swelling, traumatic injury, fracture, bleeding, and scalding. In order to further clarify the unknown chemical composition of CT, a rapid strategy based on UHPLC-Q-exactive orbitrap was established for this analysis using a Thermo Scientific Hypersil GOLDTM aQ (100 mm × 2.1 mm, 1.9 µm) chromatographic column. The mobile phase was 0.1% formic acid water-acetonitrile, with a flow rate of 0.3 mL/min and injection volume of 2 µL; for mass spectrometry, an ESI ion source in positive and negative ion monitoring modes was adopted. A total of 135 chemicals comprising 67 chlorogenic acid derivatives, 48 flavonoids, and 20 anthocyanin derivatives were identified by comparing the mass spectrum information with standard substances, public databases, and the literature, which were all discovered for the first time in this plant. This result broadly expands the chemical composition of CT, which will contribute to understanding of its effectiveness and enable quality control.


Assuntos
Medicamentos de Ervas Chinesas , Rubiaceae , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Espectrometria de Massas/métodos
6.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4214-4220, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36046912

RESUMO

This study aims to establish an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method for the determination of emodin-8-O-ß-D-glucoside(EG) and its metabolites in plasma, and to investigate the toxicokinetics(TK) behavior of them in rats. To be specific, the TK of EG and its metabolites from the first to the last administration in the repeated dose toxicity study was determined, and the kinetic parameters were calculated. The exposure of EG prototype and metabolites in rat plasma after oral administration of different doses of EG was evaluated. The result showed that the prototype of EG and its metabolites aloe-emodin-8-O-ß-D-glucoside, emodin, aloe-emodin, and hydroxyemodin could be detected in rats after oral administration of high-, medium-, and low-dose EG. The area under the curve(AUC) of the prototype and metabolites after the first and last administration was in positive correlation with the dose. The time to the maximum concentration(T_(max)) of EG and metabolites in the three administration groups was <6 h, and the longest in vivo residence time was 12 h. The T_(max) and in vivo residence time of EG were prolonged with the increase in the dose. The metabolites emodin, aloe-emodin, and hydroxyemodin all had two peaks. Both hydroxyemodin and aloe-emodin exhibited increased plasma exposure, slow metabolism, and accumulation in vivo. In addition, aloe-emodin-8-O-ß-D-glucoside and emodin disappeared with the increase in dose, suggesting the change of the metabolic pathway of EG in vivo in the case of high-dose administration. The mechanism of high-dose EG in vivo needs to be further explored. This study preliminarily elucidates the TK behavior of EG in rats, which is expected to support clinical drug use.


Assuntos
Emodina , Animais , Antraquinonas , Cromatografia Líquida de Alta Pressão/métodos , Emodina/toxicidade , Glucosídeos/toxicidade , Espectrometria de Massas , Ratos , Toxicocinética
7.
J Cell Physiol ; 235(3): 2403-2413, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31556116

RESUMO

Papillary thyroid carcinoma (PTC) is recognized as one of the most prevalent types of thyroid cancer with poor prognosis. Long noncoding RNA (lncRNA) has undergone an intensive study for their involvement in tumor treatment. This study intends to unravel the association of lncRNA SLC26A4-AS1 with PTC. Initially, PTC-related expression profiling data (GSE33630) was utilized to screen differentially expressed lncRNAs in PTC and the underlying mechanisms involved with the mitogen-activated protein kinase (MAPK) pathway. Moreover, PTC tumor tissues and paracancerous tissues were arranged to determine expressions of TP53, SLC26A4-AS1, and genes related to epithelial-mesenchymal transition (EMT) and the MAPK pathway. Furthermore, SLC26A4-AS1 was overexpressed or underexpressed and JNK was underexpressed through cell transfection to examine the effect of SLC26A4-AS1 on PTC via MAPK pathway. Besides, tumor formation in nude mice was used to verify the fore experiment. LncRNA SLC26A4-AS1 regulating TP53 had the potential to participate in PTC by regulating the MAPK pathway. SLC26A4-AS1 was expressed poorly in PTC. Notably, SLC26A4-AS1 elevated E-cadherin expression while it reduced that of ERK and Vimentin. In addition, the overexpression of SLC26A4-AS1 inactivated the MAPK pathway by promoting TP53 and decreased cell migration, proliferation, and invasion. In addition to all these effects, the overexpression of SLC26A4-AS1 promoted apoptosis of TPC-1 cells. Additionally, the overexpression of lncRNA SLC26A4-AS1 reduced xenograft tumor volume in nude mice. Furthermore, the effect of SLC26A4-AS1 overexpression was found to be promoted after the MAPK pathway inactivation. Taken together, the overexpression of lncRNA SLC26A4-AS1 coffered anti-oncogenic effects on PTC through the inactivation of the MAPK pathway.


Assuntos
Proliferação de Células/genética , RNA Longo não Codificante/genética , Transportadores de Sulfato/genética , Câncer Papilífero da Tireoide/genética , Animais , Apoptose/genética , Caderinas/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Câncer Papilífero da Tireoide/patologia
8.
J Cell Physiol ; 235(3): 2492-2505, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31565805

RESUMO

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA-599 (miR-599) on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual-luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR-599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR-559. In addition, the expression of Bax and E-cadherin was elevated while that of Hey2, Notch1, Delta-like1, Hes1, N1ICD, Jagged1, Snail, Slug, N-cadherin and Vimentin, and Bcl-2 was reduced in cells treated with upregulated miR-599 or downregulated Hey2. Moreover, miR-599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR-599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proliferação de Células/genética , MicroRNAs/genética , Proteínas Repressoras/genética , Câncer Papilífero da Tireoide/genética , Adulto , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Notch/genética , Transdução de Sinais/genética , Taxa de Sobrevida , Câncer Papilífero da Tireoide/patologia
9.
Zhongguo Zhong Yao Za Zhi ; 45(2): 412-417, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-32237326

RESUMO

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.


Assuntos
Antraquinonas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Fígado/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Humanos , Fígado/enzimologia , Rizoma
10.
Acta Pharmacol Sin ; 40(7): 938-948, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30560903

RESUMO

L-Carnosine (ß-alanyl-L-histidine) is a naturally occurring dipeptide distributed in various organs of mammalians. We previously showed that carnosine inhibited proliferation of human gastric cancer cells through targeting both mitochondrial bioenergetics and glycolysis pathway. But the mechanism underlying carnosine action on mitochondrial bioenergetics of tumor cells remains unclear. In the current study we investigated the effect of carnosine on the growth of human gastric cancer SGC-7901 cells in vitro and in vivo. We firstly showed that hydrolysis of carnosine was not a prerequisite for its anti-gastric cancer effect. Treatment of SGC-7901 cells with carnosine (20 mmol/L) significantly decreased the activities of mitochondrial respiratory chain complexes I-IV and mitochondrial ATP production, and downregulated 13 proteins involved in mitochondrial bioenergetics. Furthermore, carnosine treatment significantly suppressed the phosphorylation of Akt, while inhibition of Akt activation with GSK690693 significantly reduced the localization of prohibitin-1 (PHB-1) in the mitochondria of SGC-7901 and BGC-823 cells. In addition, we showed that silencing of PHB-1 gene with shRNA markedly reduced the mitochondrial PHB-1 in SGC-7901 cells, and significantly decreased the colony formation capacity and growth rate of the cells. In SGC-7901 cell xenograft nude mice, administration of carnosine (250 mg kg/d, ip, for 3 weeks) significantly inhibited the tumor growth and decreased the expression of mitochondrial PHB-1 in tumor tissue. Taken together, these results suggest that carnosine may act on multiple mitochondrial proteins to down-regulate mitochondrial bioenergetics and then to inhibit the growth and proliferation of SGC-7901 and BGC-823 cells.


Assuntos
Antineoplásicos/uso terapêutico , Carnosina/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Carnosina/farmacologia , Linhagem Celular Tumoral , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Humanos , Camundongos Nus , Proteínas Mitocondriais/metabolismo , Proibitinas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Repressoras/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Zhongguo Zhong Yao Za Zhi ; 44(18): 4043-4047, 2019 Sep.
Artigo em Zh | MEDLINE | ID: mdl-31872743

RESUMO

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.


Assuntos
Apigenina/química , Bilirrubina/química , Interações Medicamentosas , Microssomos Hepáticos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Glucuronosiltransferase/metabolismo , Humanos , Ligação de Hidrogênio
12.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2367-2372, 2019 Jun.
Artigo em Zh | MEDLINE | ID: mdl-31359665

RESUMO

To evaluate the hepatotoxicity risks of physcion on the basis of the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1(UGT1A1 enzyme). The monomers were added into the rat liver microsomes to test the hepatotoxicity by using bilirubin as UGT1A1 enzyme substrate, with apparent inhibition constant K_i as the evaluation index. Liver microsome incubation in vitro was adopted to initiate phase Ⅱ metabolic reaction and investigate the inhibitory effect of physcion. Then the phase Ⅰ and Ⅱ metabolic reactions were initiated to investigate the comprehensive inhibition of metabolites and prototype components. The results showed that when only the phase Ⅱ reaction was initiated, physcion directly acted on the UGT1A1 enzyme in a prototype form, exhibited weak inhibition and the inhibition type was mixed inhibition; When the phase Ⅰ and Ⅱ reactions were initiated simultaneously, the inhibitory effects of physcion on UGT1A1 enzyme became strong and the inhibition type was mixed inhibition, suggesting that physcion had phase Ⅰ and Ⅱ metabolic processes, and the metabolites had strong inhibitory effect on UGT1A1 enzyme. This experiment preliminarily proved that the metabolites of physcion may be the main components to induce hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Emodina/análogos & derivados , Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Animais , Emodina/toxicidade , Cinética , Ratos
13.
Prenat Diagn ; 37(12): 1219-1224, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29025195

RESUMO

OBJECTIVES: To assess the chromosomal and subchromosomal anomalies in small for gestational age (SGA) fetuses with no additional structural anomalies and their clinical outcomes. METHODS: This study retrospectively reviewed the 128 SGA fetuses with no additional anomalies and underwent genetic testing with karyotyping and chromosomal microarray analysis (CMA). Stratified analysis was performed according to the existence of maternal risk factors for SGA (yes or no), gestational age at onset (before or after 32 weeks), presence of oligohydraminos (yes or no), and umbilical artery Doppler flow (normal or abnormal). RESULTS: Chromosomal anomalies were identified in 6 (4.7%) SGA fetuses and pathogenic subchromosomal anomalies in 4 (3.1%) by microarray analysis. Chromosomal and subchromosomal anomalies were more frequently observed in cases with oligohydraminos (P = .017) and with early-onset SGA (P = .042). No differences were observed in relation to the existence of maternal risk factors and abnormal umbilical artery Doppler flow. Overall survival rate was 75.0% with different rates in the early and the late onset group (P < .001). CONCLUSIONS: There is a 3.3% incremental yield of subchromosomal anomalies in CMA above karyotyping in SGA fetuses. Chromosomal microarray analysis is recommended in SGA fetuses with no additional structural anomalies, especially coexisting with oligohydraminos and being early onset.


Assuntos
Aberrações Cromossômicas , Retardo do Crescimento Fetal/genética , Diagnóstico Pré-Natal , Adulto , China/epidemiologia , Feminino , Retardo do Crescimento Fetal/mortalidade , Humanos , Análise em Microsséries , Gravidez , Estudos Retrospectivos , Adulto Jovem
14.
Plant Mol Biol ; 90(1-2): 49-62, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26482477

RESUMO

Salt is a major environmental stress factor that can affect rice growth and yields. Recent studies suggested that members of the AP2/ERF domain-containing RAV (related to ABI3/VP1) TF family are involved in abiotic stress adaptation. However, the transcriptional response of rice RAV genes (OsRAVs) to salt has not yet been fully characterized. In this study, the expression patterns of all five OsRAVs were examined under salt stress. Only one gene, OsRAV2, was stably induced by high-salinity treatment. Further expression profile analyses indicated that OsRAV2 is transcriptionally regulated by salt, but not KCl, osmotic stress, cold or ABA (abscisic acid) treatment. To elucidate the regulatory mechanism of the stress response at the transcriptional level, we isolated and characterized the promoter region of OsRAV2 (P OsRAV2 ). Transgenic analysis indicated that P OsRAV2 is induced by salt stress but not osmotic stress or ABA treatment. Serial 5' deletions and site-specific mutations in P OsRAV2 revealed that a GT-1 element located at position -664 relative to the putative translation start site is essential for the salt induction of P OsRAV2 . The regulatory function of the GT-1 element in the salt induction of OsRAV2 was verified in situ in plants with targeted mutations generated using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system. Taken together, our results indicate that the GT-1 element directly controls the salt response of OsRAV2. This study provides a better understanding of the putative functions of OsRAVs and the molecular regulatory mechanisms of plant genes under salt stress.


Assuntos
Oryza/genética , Proteínas de Plantas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Cloreto de Sódio/farmacologia , Adaptação Fisiológica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oryza/efeitos dos fármacos , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Tolerância ao Sal , Estresse Fisiológico
15.
Bioorg Med Chem Lett ; 26(3): 799-803, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26777629

RESUMO

Four new alkenes (1-4), and six known alkenes (5-12) were isolated from Murraya koenigii (L.) Spreng. Their structures were elucidated on the basis of spectroscopic analyses and references. Compounds (1-12) were evaluated for antioxidative activities. Among them, compounds 1, 2, 4, and 7 exhibited significant antioxidative activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50=21.4-49.5 µM. The known compounds (5-12) were isolated from this plant for the first time.


Assuntos
Alcenos/química , Antioxidantes/química , Murraya/química , Extratos Vegetais/química , Alcenos/isolamento & purificação , Antioxidantes/isolamento & purificação , Dicroísmo Circular , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Conformação Molecular , Murraya/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo
16.
Prenat Diagn ; 36(8): 766-74, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27315788

RESUMO

OBJECTIVE: To evaluate whether discrepant copy number variations (CNVs) contribute to the risk for discordant congenital anomalies in monochorionic diamniotic (MCDA) twins. METHODS: We conducted a parallel testing using both G-banding for standard karyotyping and chromosomal microarray analysis (CMA) with Affymetrix CytoScan HD array in MCDA twins with discordant malformations. RESULTS: During the study period, 193 MCDA twins with discordant malformations were detected and followed up. Multiple anomalies and cardiac defects were detected most frequently among the fetuses with malformations. Among all the 119 MCDA twins that were successfully performed fetal karyotyping, discordance of chromosomal aberrations were identified in nine cases, including one with discordant trisomy 18, seven with discordant monosomy X, one twin with 47, XXY and the co-twin with 45, X [7]/46, XY[43]. CMA revealed pathological CNVs in four out of the 110 fetuses with normal karyotype and the detection rate of uncertain clinical significance was 3.6% (4/110). Discordance of CNVs was detected in 5.5% (3/55) among the 55 MCDA twins with normal karyotype. Monozygosity was confirmed in all the 61 MCDA twins that were performed CMA. CONCLUSIONS: Large whole chromosome abnormalities are more common between discordant twins rather than smaller CNVs in this study. © 2016 John Wiley & Sons, Ltd.


Assuntos
Transtornos Cromossômicos/genética , Anormalidades Congênitas/genética , Variações do Número de Cópias de DNA/genética , Doenças em Gêmeos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 18/genética , Anormalidades Congênitas/diagnóstico por imagem , Doenças em Gêmeos/diagnóstico , Feminino , Humanos , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Análise em Microsséries , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomía do Cromossomo 18 , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Adulto Jovem
17.
Gynecol Obstet Invest ; 81(6): 552-558, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27035917

RESUMO

AIMS: To review pregnancy outcomes, complication rates and neonatal neural development of selective termination procedures for complicated monochorionic (MC) twins. METHODS: This was a retrospective review of the pregnancies that underwent selective reduction with radiofrequency ablation (RFA) and bipolar cord coagulation (BCC) in our institution. RESULTS: Forty-eight cases underwent selective reduction with BCC and the remaining 45 with RFA. Overall survival was not statistically different between the RFA and BCC groups (71.1 and 62.5%, p = 0.379). With regard to the indications, the survival rates were not significantly different for twin to twin transfusion syndrome, twin reversed arterial perfusion, discordant anomalies and selective intrauterine growth restriction. Preterm premature rupture of membrane was not statistically different between the BCC and RFA groups (47.9 and 33.3%, p = 0.153). Five foetuses presented with abnormal middle cerebral artery-peak systolic velocity in the BCC group and 4 in the RFA group (p = 0.829). In the BCC group, neurological injury was detected in 2 neonates, presenting with cerebral dysplasia on MR scanning. In the RFA group, intracranial haemorrhage Grade III was detected in one neonate with cranial ultrasound (p = 0.607). CONCLUSIONS: Overall survival and complication rates following selective reduction in complicated MC twin pregnancies is similar irrespective of whether the reduction was performed using RFA or BCC. Key Message: It seems that selective reduction in MC pregnancies with RFA does not carry a significant decrease in the overall survival and complication rates than the cases with BCC. According to our data, neurodevelopmental impairment of the co-twins is relatively seldom after selective reduction.


Assuntos
Doenças em Gêmeos/cirurgia , Sistema Nervoso/crescimento & desenvolvimento , Redução de Gravidez Multifetal/métodos , Gravidez de Gêmeos , Cordão Umbilical/cirurgia , Ablação por Cateter , Eletrocoagulação , Feminino , Humanos , Doenças do Sistema Nervoso/etiologia , Gravidez , Resultado da Gravidez , Redução de Gravidez Multifetal/efeitos adversos , Estudos Retrospectivos
18.
Biomed Environ Sci ; 29(2): 148-52, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27003173

RESUMO

We evaluated the antimutagenic effects of 10 kinds of bioactive phytochemicals and some phytochemical combinations against methotrexate (MTX)-induced genotoxicity by the umu test in Salmonella typhimurium TA1535/pSK1002 combined with a micronucleus assay. We observed that allicin, proanthocyanidins, polyphenols, eleutherosides, and isoflavones had higher antimutagenic activities than the other five types of bioactive phytochemicals. At the highest dose tested, MTX-induced genotoxicity was inhibited by 25%-75%. Kunming mice treated by MTX along with bioactive phytochemical combinations showed significant reduction in micronucleus induction and sperm abnormality rate (P<0.01). These results indicate that bioactive phytochemical combinations can be potentially used as new cytoprotectors.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Citoproteção , Metotrexato/efeitos adversos , Fitoterapia , Extratos Vegetais , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos , Testes para Micronúcleos , Distribuição Aleatória , Salmonella typhimurium
19.
J Asian Nat Prod Res ; 18(5): 436-42, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26982201

RESUMO

Two new prenylated phloroglucinol derivatives (1-2), and a known compound furohyperforim isomer 2 (3), were isolated from the aerial parts of Hypericum scabrum. Their structures were elucidated by various spectroscopic methods, including MS, IR, UV, and NMR.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Hypericum/química , Floroglucinol/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Floroglucinol/química , Prenilação , Estereoisomerismo
20.
J Asian Nat Prod Res ; 18(9): 813-22, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27139982

RESUMO

Four new dianthrone glycosides, named polygonumnolides C1-C4 (1-4), were isolated from the dried roots of Polygonum multiflorum Thunb, together with two known emodin dianthrones (5-6). Their hepatotoxicities were evaluated against L-02 cell lines. Compounds 1-4 showed weak hepatotoxicity against L-02 cell lines with IC50 values of 313.05, 205.20, 294.20, and 207.35 µM, respectively.


Assuntos
Antracenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Glicosídeos/isolamento & purificação , Fígado/efeitos dos fármacos , Polygonum/química , Antracenos/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Emodina/química , Glicosídeos/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Estereoisomerismo
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