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1.
Bioorg Chem ; 153: 107900, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39442460

RESUMO

The discovery and utilization of new fluorescent chromophore is indispensable to exploit high performance probes for biological research. Stokes shift is one of the most important properties of chromophore accounting for super-resolution fluorescence imaging. Intramolecular charge transfer (ICT) is one of the fundamental mechanisms for fluorescence that accompanied by large Stokes shifts. Based on the conformational changes between ground and excited states, ICT models can be divided into two types: conformation-steady ICT, whose conformation remains unchanged, and conformation-changeable ICT, which is characterized by the rotation of the chromophore around an axis upon excitation. Herein, we report a new chromophore whose donor and acceptor parts took a butterfly geometry with a dihedral angle of 21° in ground state and a planar conformation upon photo excitation. The bent conformation might be ascribed to the extra conjugated double bond, which made the coplanarity of the chromophore in ground state get worse. The chromophore shows a remarkable Stokes shift over 150 nm and a high fluorescence quantum yieldof 0.62. The limit of detection is 41 nM, which enabled the imaging of basal as well as induced OCl- in different cells. Moreover, the pronounced spectroscopic properties ensure the in vivo monitoring of OCl- in arthritic mice. This finding would shed light on the exploitation of small molecule probes based on new fluorescence chromophore for precise biological imaging.

2.
Bioorg Chem ; 138: 106623, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37295240

RESUMO

Fangchinoline (Fan) are extracted from the traditional Chinese medicine Stephania tetrandra S., which is a bis-benzyl isoquinoline alkaloids with anti-tumor activity. Therefore, 25 novel Fan derivatives have been synthesized and evaluated for their anti-cancer activity. In CCK-8 assay, these fangchinoline derivatives displayed higher proliferation inhibitory activity on six tumor cell lines than the parental compound. Compared to the parent Fan, compound 2h presented the anticancer activity against most cancer cells, especially A549 cells, with an IC50 value of 0.26 µM, which was 36.38-fold, and 10.61-fold more active than Fan and HCPT, respectively. Encouragingly, compound 2h showed low biotoxicity to the human normal epithelial cell BEAS-2b with an IC50 value of 27.05 µM. The results indicated compound 2h remarkably inhibited the cell migration by decreasing MMP-2 and MMP-9 expression and inhibited the proliferation of A549 cells by arresting the G2/M cell cycle. Meanwhile, compound 2h could also induce A549 cell apoptosis by promoting endogenous pathways of mitochondrial regulation. In nude mice presented that the growth of tumor tissues was markedly inhibited by the consumption of compound 2h in a dose-dependent manner, and it was found that compound 2h could inhibit the mTOR/PI3K/AKT pathway in vivo. In docking analysis, high affinity interaction between 2h and PI3K was responsible for drastic kinase inhibition by the compound. To conclude, this derivative compound may be useful as a potent anti-cancer agent for treatment of NSCLC.


Assuntos
Antineoplásicos , Benzilisoquinolinas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Neoplasias Pulmonares/metabolismo , Proliferação de Células , Benzilisoquinolinas/farmacologia , Benzilisoquinolinas/uso terapêutico , Linhagem Celular Tumoral , Apoptose , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
3.
Microb Pathog ; 165: 105489, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35306153

RESUMO

The antibacterial and antibiofilm mechanisms of ultrasound combined with chlorogenic acid treatment for Salmonella enteritidis under biofilm and planktonic condition were investigated. S. enteritidis under biofilm and planktonic cells were treated with ultrasound, chlorogenic acid, and their combination for 5, 10, 20, 30, and 60 min. Results showed that the combined treatments exhibited synergistic effects that inactivated the S. enteritidis biofilm and planktonic cells. The nucleic acids and ATP leakage and CLSM imagines showed that the combining chlorogenic acid and ultrasound treatment significantly increased the permeability of the S. enteritidis cell membrane. SEM indicated that the combining chlorogenic acid and ultrasound treatment quickly destroyed the integrity of the S. enteritidis cell membrane, and the activity of respiratory chain dehydrogenase sharply decreased. Additionally, the amounts of polysaccharides in the S. enteritidis biofilms significantly decreased after the combined treatments. Hence, the combining chlorogenic acid and ultrasound treatment have potential applications in food preservation.


Assuntos
Plâncton , Salmonella enteritidis , Antibacterianos/farmacologia , Biofilmes , Ácido Clorogênico/farmacologia
4.
Bioorg Chem ; 126: 105916, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35687986

RESUMO

Hyperuricemia is a common metabolic disease with a series of complications. Nuciferine, a typical aporphine alkaloid natural compound extracted from the leaves of Nelumbo nucifera Gaertn., was confirmed to have an antihyperuricemia effect. In the present study, 30 novel nuciferine derivatives were designed and synthesized. The effects of all derivatives on the regulation of URAT1 were studied in a uric acid-induced HK-2 cell model with benzbromarone as a positive control. The results indicated that Compound 1j showed the optimal URAT1 inhibitory activity through repressing PI3K/Akt pathway in HK-2 cells and the inhibitory effect was similar to that of benzbromarone. In addition, in vivo experiments demonstrated that Compound 1j could reduce uric acid levels and ameliorate kidney damage in hyperuricemic mice. On the one hand, Compound 1j could inhibit the expression of URAT1 and GLUT9 to increase the uric acid excretion index. On the other hand, Compound 1j could regulate the TLR4/IκBα/NF-κB signaling pathway to reduce the levels of inflammatory cytokines, thereby alleviating kidney damage. Meanwhile, a molecular docking assay revealed the potential molecular binding power (-9.79 kcal/mol) between Compound 1j and URAT1, which was more tightly bound than the lead compound nuciferine (-7.44 kcal/mol). Based on these results, Compound 1j may be a future drug for the development of new potential antihyperuricemia and nephroprotective drug candidates.


Assuntos
Aporfinas , Hiperuricemia , Transportadores de Ânions Orgânicos , Animais , Aporfinas/farmacologia , Benzobromarona/efeitos adversos , Hiperuricemia/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Ácido Úrico
5.
Foodborne Pathog Dis ; 19(1): 70-79, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34883029

RESUMO

Klebsiella pneumoniae is an important foodborne pathogen with high biofilm-forming ability, which is continuously detected in food products in recent years. The antibacterial and antibiofilm activities and mechanism of ultrasonication in combination with heat treatment against K. pneumoniae were studied. K. pneumoniae planktonic and biofilm cells were treated with ultrasound (US), mild heat treatment (HT50, HT60, and HT70), and combinations of US and mild heat treatment (UH50, UH60, and UH70) for 5, 10, 20, 30, and 60 min. Results showed that the combination of US and mild heat treatment was more effective in inactivating K. pneumoniae planktonic and biofilm cells than the single treatment by counting viable bacteria. In addition, confocal laser scanning microscopy, scanning electron microscopy, and analysis of leakage of intracellular substances have revealed that the combination treatment effectively damaged the integrity of bacterial cell membrane and increased cell permeability, which led to the quick release of adenosine triphosphate (ATP) and macromolecular substances of nucleic acids and proteins. Moreover, the activities of respiratory chain dehydrogenase in planktonic and biofilm cells significantly decreased after UH treatment. The results indicated that ultrasonication and mild heat treatment had a synergistic effect on the inactivation of K. pneumoniae planktonic and biofilm cells by damaging the cell membrane and inhibiting intercellular cell respiration.


Assuntos
Galinhas , Klebsiella pneumoniae , Animais , Antibacterianos/farmacologia , Biofilmes , Corantes , Temperatura Alta , Carne , Testes de Sensibilidade Microbiana
6.
Angew Chem Int Ed Engl ; 61(9): e202116085, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-34981626

RESUMO

Luminescent metal halides have attracted considerable attention in next-generation solid-state lighting because of their superior optical properties and easy solution processibility. Herein, we report a new class of highly efficient and dual-band-tunable white-light emitters based on Bi3+ /Te4+ co-doped perovskite derivative Cs2 SnCl6 microcrystals. Owing to the strong electron-phonon coupling and efficient energy transfer from Bi3+ to Te4+ , the microcrystals exhibited broad dual-band white-light emission originating from the inter-configurational 3 P0,1 →1 S0 transitions of Bi3+ and Te4+ , with good stability and a high photoluminescence (PL) quantum yield of up to 68.3 %. Specifically, a remarkable transition in Bi3+ -PL lifetime from milliseconds at 10 K to microseconds at 300 K was observed, as solid evidence for the isolated Bi3+ emission. These findings provide not only new insights into the excited-state dynamics of Bi3+ and Te4+ in Cs2 SnCl6 , but also a general approach to achieve single-composition white-light emitters based on lead-free metal halides through ns2 -metal ion co-doping.

7.
Angew Chem Int Ed Engl ; 61(26): e202201993, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35438824

RESUMO

All-inorganic lead-free perovskite-derivative metal halides have shown great promise in optoelectronics, however, it remains challenging to realize efficient near-infrared (NIR) luminescence in these materials. Herein, we report a novel strategy based on Te4+ /Ln3+ (Ln=Er, Nd, and Yb) co-doping to achieve efficient NIR luminescence in vacancy-ordered double perovskite Cs2 ZrCl6 phosphors, which are excitable by a low-cost near-ultraviolet light-emitting diode (LED) chip. Through sensitization by the spin-orbital allowed 1 S0 →3 P1 transition of Te4+ , intense and multi-wavelength NIR luminescence originating from the 4f→4f transitions of Er3+ , Nd3+ , and Yb3+ was acquired, with a quantum yield of 6.1 % for the Er3+ emission. These findings provide a general approach to achieve efficient NIR emission in lead-free metal halides through ns2 -metal and lanthanide ion co-doping, thereby opening up a new avenue for exploring NIR-emitting perovskite derivatives towards versatile applications such as NIR-LEDs and bioimaging.

8.
Bioorg Chem ; 116: 105321, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34500305

RESUMO

Hyperuricemia is a principal factor mediating gout and kidney damage, and xanthine oxidase (XOD) is a key enzyme in the pathogenesis of hyperuricemia. In this context, a series of geniposide derivatives were designed and synthesized, and antihyperuricemic and nephroprotective effects of all derivatives was evaluated in vitro and in vivo. Compound 2e emerged as the most potent XOD inhibitor, with an IC50 value of 6.67 ± 0.46 µM. Simultaneously, cell viability, ROS generation, and SOD levels assay showed that compound 2e could repair the damage of HKC cells by inhibiting the oxidative stress response. The results of the study indicated compound 2e significantly decreased uric acid levels by inhibiting the XOD activity, and repaired kidney damage by inhibiting the expression of TLR4/TLR2/MyD88/NF-κB and NALP3/ASC/caspase-1 signaling pathways. Enzyme inhibition kinetics suggested that compound 2e functioned via reversible mixed competitive inhibition. Moreover, a molecular docking study was performed to gain insight into the binding mode of compound 2e with XOD. These results suggest that geniposide derivatives were potential to be developed into a novel medicine to reveal healthy benefits in natural prevention and reduction risk of hyperuricemia and kidney damage.


Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Supressores da Gota/farmacologia , Hiperuricemia/tratamento farmacológico , Iridoides/farmacologia , Xantina Oxidase/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Supressores da Gota/síntese química , Supressores da Gota/química , Humanos , Hiperuricemia/metabolismo , Iridoides/síntese química , Iridoides/química , Estrutura Molecular , Relação Estrutura-Atividade , Xantina Oxidase/metabolismo
9.
Bioorg Chem ; 109: 104694, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33601141

RESUMO

Cancer treatment is one of the major public health issues in the world. Tetrandrine (Tet) and fangchinoline (d-Tet) are two bis-benzyl isoquinoline alkaloids extracted from Stephania tetrandra S. Moore, and their antitumor activities have been confirmed. However, the effective dose of Tet and d-Tet were much higher than that of the positive control and failed to meet clinical standards. Therefore, in this study, as a continuation of our previous work to study and develop high-efficiency and low-toxic anti-tumor lead compounds, twenty new Tet and d-Tet derivatives were designed, synthesized and evaluated as antitumor agents against six cancer cell lines (H460, H520, HeLa, HepG-2, MCF-7, SW480 cell lines) and BEAS-2B normal cells by CCK-8 analysis. Ten derivatives showed better cytotoxic effects than the parent fangchinoline, of which 4g showed the strongest cell growth inhibitory activity with an IC50 value of 0.59 µM against A549 cells. Subsequently, the antitumor mechanism of 4g was studied by flow cytometry, Hoechst 33258, JC-1 staining, cell scratch, transwell migration, and Western blotting assays. These results showed that compound 4g could inhibit A549 cell proliferation by arresting the G2/M cell cycle and inhibiting cell migration and invasion by reducing MMP-2 and MMP-9 expression. Meanwhile, 4g could induce apoptosis of A549 cells through the intrinsic pathway regulated by mitochondria. In addition, compound 4g inhibited the phosphorylation of PI3K, Akt and mTOR, suggesting a correlation between blocking the PI3K/Akt/mTOR pathway and the above antitumor activities. These results suggest that compound 4g may be a future drug for the development of new potential drug candidates against lung cancer.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzilisoquinolinas/química , Desenho de Fármacos , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Humanos , Estrutura Molecular
10.
Gastroenterology ; 156(8): 2281-2296.e6, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30779922

RESUMO

BACKGROUND & AIMS: Levels of microRNA 31 (MIR31) are increased in intestinal tissues from patients with inflammatory bowel diseases and colitis-associated neoplasias. We investigated the effects of this microRNA on intestinal inflammation by studying mice with colitis. METHODS: We obtained colon biopsy samples from 82 patients with ulcerative colitis (UC), 79 patients with Crohn's disease (CD), and 34 healthy individuals (controls) at Shanghai Tenth People's Hospital. MIR31- knockout mice and mice with conditional disruption of Mir31 specifically in the intestinal epithelium (MIR31 conditional knockouts) were given dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. We performed chromatin immunoprecipitation and luciferase assays to study proteins that regulate expression of MIR31, including STAT3 and p65, in LOVO colorectal cancer cells and organoids derived from mouse colon cells. Partially hydrolyzed alpha-lactalbumin was used to generate peptosome nanoparticles, and MIR31 mimics were loaded onto their surface using electrostatic adsorption. Peptosome-MIR31 mimic particles were encapsulated into oxidized konjac glucomannan (OKGM) microspheres, which were administered by enema into the large intestines of mice with DSS-induced colitis. Intestinal tissues were collected and analyzed by histology and immunohistochemistry. RESULTS: Levels of MIR31 were increased in inflamed mucosa from patients with CD or UC, and from mice with colitis, compared with controls. STAT3 and nuclear factor-κB activated transcription of MIR31 in colorectal cancer cells and organoids in response to tumor necrosis factor and interleukin (IL)6. MIR31-knockout and conditional-knockout mice developed more severe colitis in response to DSS and TNBS, with increased immune responses, compared with control mice. MIR31 bound to 3' untranslated regions of Il17ra and Il7r messenger RNAs (RNAs) (which encode receptors for the inflammatory cytokines IL17 and IL7) and Il6st mRNA (which encodes GP130, a cytokine signaling protein). These mRNAs and proteins were greater in MIR31-knockout mice with colitis, compared with control mice; MIR31 and MIR31 mimics inhibited their expression. MIR31 also promoted epithelial regeneration by regulating the WNT and Hippo signaling pathways. OKGM peptosome-MIR31 mimic microspheres localized to colonic epithelial cells in mice with colitis; they reduced the inflammatory response, increased body weight and colon length, and promoted epithelial cell proliferation. CONCLUSIONS: MIR31, increased in colon tissues from patients with CD or UC, reduces the inflammatory response in colon epithelium of mice by preventing expression of inflammatory cytokine receptors (Il7R and Il17RA) and signaling proteins (GP130). MIR31 also regulates the WNT and Hippo signaling pathways to promote epithelial regeneration following injury. OKGM peptosome-MIR31 microspheres localize to the colon epithelium of mice to reduce features of colitis. Transcript Profiling: GSE123556.


Assuntos
Biomarcadores/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/patologia , Mucosa Intestinal/metabolismo , MicroRNAs/metabolismo , Regeneração/fisiologia , Animais , Biópsia por Agulha , Estudos de Casos e Controles , China , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Microesferas , RNA Mensageiro/metabolismo , Distribuição Aleatória , Transdução de Sinais
11.
Bioorg Chem ; 94: 103431, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759658

RESUMO

The isolation and modification of natural products play an important role in the synthesis of anti-tumor drugs for the treatment of cancer. The present study was designed to evaluate the effects of fangchinoline derivatives against cancer cells. In vitro cytotoxicity of all derivatives against five cancer cell lines (A549, Hela, HepG-2, MCF-7 and MDA-MB-231 cell lines) and HL-7702 normal cells was assessed using the CCK-8 assay, and the results showed that most of the synthesized compounds displayed better cytotoxic effects on all the tested cells compared to that of the parent fangchinoline. In particular, compound 3i had the strongest inhibitory effect on cell proliferation, with an IC50 value of 0.61 µM against A549 cells. Compared with fangchinoline and HCPT (hydroxycamptothecine), the anti-proliferative activity of compound 3i was significantly increased. More interestingly, compound 3i had slight toxic side effects on normal cells, with an IC50 value of 27.53 µM. Moreover, the cell viability and cell cycle assays revealed that compound 3i inhibited A549 cell proliferation and arrested A549 cells at the G2/M-phase. The apoptosis-inducing effects of compound 3i and the associated molecular mechanisms were assessed using flow cytometry, cell staining, reactive oxygen species assays, RT-qPCR and Western blot analysis. These results suggested that compound 3i induces apoptosis through a mitochondria-mediated intrinsic pathway. This study revealed that compound 3i is a promising candidate for future development as an anti-tumor drug.


Assuntos
Antineoplásicos/farmacologia , Benzilisoquinolinas/farmacologia , Desenho de Fármacos , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Benzilisoquinolinas/síntese química , Benzilisoquinolinas/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
12.
J Sci Food Agric ; 100(12): 4495-4503, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32399976

RESUMO

BACKGROUND: Steam explosion is increasingly being used in the food processing industry as an efficient pretreatment technology. It is currently being used to pretreat adzuki beans at a pressure of 0.25-1.0 Mpa for 30 s and 90 s. In this study, the total polyphenol (TP) content in adzuki beans, including free polyphenols (FP) and bound polyphenols (BP), and their antioxidant activity, were determined after steam explosion treatment. RESULTS: The results showed that steam explosion can form large cavities and intercellular spaces, which aid the release of polyphenols. After steam explosion, the FP, BP, and TP content increased. The antioxidant capacity of FP and BP also increased, which demonstrated that there was a positive correlation between the polyphenol content and antioxidant capacity. Compounds of FP and BP were further identified by high-performance liquid chromatography (HPLC). Protocatechin was the main ingredient in FP and BP, and protocatechin was higher in FP. Isoquercetin only exists in FP, and caffeic acid only in BP. After steam explosion, an increase in the protocatechin, catechin, and epicatechin content was detected in FP and BP. The phenolic compound and antioxidant capacity yield was increased at a pressure of 0.25-0.75 Mpa, however it decreased at 1.0 Mpa. A pressure of 0.75 Mpa for 90 s is the optimal condition for polyphenol separation in adzuki beans. CONCLUSION: A proper and reasonable steam explosion can effectively increase the release of phenolics and enhance the antioxidant capacity in adzuki beans. © 2020 Society of Chemical Industry.


Assuntos
Antioxidantes/isolamento & purificação , Manipulação de Alimentos/métodos , Extratos Vegetais/isolamento & purificação , Polifenóis/isolamento & purificação , Vigna/química , Antioxidantes/análise , Cromatografia Líquida de Alta Pressão , Manipulação de Alimentos/instrumentação , Extratos Vegetais/análise , Polifenóis/análise , Sementes/química , Vapor
13.
Chem Biodivers ; 13(6): 645-71, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27161126

RESUMO

Ligularia speices are widely used in Asian folk medicines for the treatment of various human diseases. Eremophilane-type sesquiterpenes are abundant and typical secondary metabolites found in this genus. Over 500 eremophilanes reported from members of Ligularia are reviewed in this article together with bioactivity data in an effort to highlight the development in this field.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Asteraceae/química , Sesquiterpenos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Bactérias/efeitos dos fármacos , Linhagem Celular , Células Hep G2 , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
14.
J Sci Food Agric ; 96(10): 3393-400, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26538333

RESUMO

BACKGROUND: Plant polyphenols are rich in blueberries that have a wide range of properties beneficial to human health. There are two types, according to the solubility of polyphenols, which were defined as extractable polyphenols (EPP) and non-extractable polyphenols (NEPP), respectively. At present, in most of reports, 'total polyphenol' refers only to EPP excluding NEPP. In this paper, the effects of EPP and NEPP on lipopolysaccharides (LPS) induced production of nitric oxide (NO) and gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells via nuclear factor-κB (NF-κB) signalling pathway were compared. RESULTS: The results showed that EPP and NEPP from blueberries significantly inhibited the LPS-induced production of NO and gene expression of iNOS and COX-2 in cells. The constitutive level of p65 sub-unit of NF-κB was obviously detected after the treatments with EPP or NEPP. By contrast, the level of phosphorylated p65 (P-p65) was strongly inhibited by EPP or NEPP. EPP had a stronger inhibition on the gene expression of iNOS and COX-2 than that of NEPP. CONCLUSION: These findings of inhibition of iNOS and COX-2 mRNA expression through the suppression of NF-κB suggest that EPP and ENPP from blueberries have significant anti-inflammatory effect and may be a potential medicine. © 2015 Society of Chemical Industry.


Assuntos
Mirtilos Azuis (Planta) , Ciclo-Oxigenase 2/genética , Macrófagos/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Polifenóis/farmacologia , Animais , Anti-Inflamatórios , Frutas/química , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Polifenóis/isolamento & purificação , Células RAW 264.7 , RNA Mensageiro/análise , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
15.
Zhong Yao Cai ; 38(3): 514-7, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-26495651

RESUMO

OBJECTIVE: To investigate the chemical constituents in the ethanol extract from the whole plant of Euphorbia lunulata. METHODS: The whole plant of Euphorbia lunulata was extracted by 95% ethanol, then partitioned by system solvents with different polarity. The ethyl acetate and n-butyl alcohol extracts were separated on silica gel, Sephadex LH-20,and MCI columns. The isolated compounds were determined by detailed analysis of their spectral data. RESULTS: Twelve compounds were isolated and identified from the ethyl acetate and n-butyl alcohol extracts of Euphorbia lunulata and the structures were identified as 7ß-methoxy-stigmast-5-ene-3ß-ol (1), 7ß-methoxy-stigmast-5-ene-3ß,22ß-diol(2), asperglaucide(3), moscatin (4), p-hydroxybenzoic acid (5),3-methoxy-4-hydroxy benzoic acid(6), erigeside C(7),5,7,4'-trihydroxy flavanone(8), kaempferol(9), quercetin(10), corosolic acid(11) and acacetin (12). CONCLUSION: All compounds except for 9 and 10 are reported from this plant for the first time.


Assuntos
Euphorbia/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Quempferóis , Compostos Fitoquímicos/isolamento & purificação , Quercetina
16.
J Antimicrob Chemother ; 69(2): 463-70, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24084636

RESUMO

OBJECTIVES: The objective of this study was to estimate the population pharmacokinetics of voriconazole, to identify the factors influencing voriconazole pharmacokinetics and to identify optimal dosage regimens for attaining target pharmacokinetic/pharmacodynamic indices against Aspergillus and Candida infections in patients with invasive fungal infections (IFIs). METHODS: To prospectively quantify the relationships between the pharmacokinetic parameters of voriconazole and covariates, a population pharmacokinetic analysis was conducted on pooled data from 406 samples taken from 151 patients with IFIs. Voriconazole plasma concentrations were measured by HPLC. The following covariates were tested: demographic factors, laboratory data, concomitant medications and CYP2C19 genotype. Monte Carlo simulation was used to evaluate the effectiveness of the currently recommended dosage regimen and to design an optimized pharmacodynamic dosage strategy for voriconazole. RESULTS: The data were appropriately fit by a one-compartment model with first-order absorption and elimination. The voriconazole clearance (CL) was 6.95 L/h, the volume of distribution (V) was 200 L and the oral bioavailability (F) was 89.5%. CL was significantly associated with age, the serum concentration of alkaline phosphatase and the CYP2C19 genotype. Based on the results of the Monte Carlo stimulation, we concluded that Aspergillus infections could be treated effectively with 200 mg of voriconazole administered intravenously or orally twice daily and that Candida infections could be treated with 300 mg administered orally twice daily or with 200 mg administered intravenously twice daily. CONCLUSIONS: This study showed that optimal voriconazole dosage regimens could be determined successfully with prospective population pharmacokinetic analyses and Monte Carlo simulations.


Assuntos
Antifúngicos/farmacocinética , Aspergilose/tratamento farmacológico , Candidíase Invasiva/tratamento farmacológico , Método de Monte Carlo , Pirimidinas/farmacocinética , Triazóis/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Aspergilose/sangue , Candidíase Invasiva/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirimidinas/administração & dosagem , Triazóis/administração & dosagem , Voriconazol
17.
Tumour Biol ; 35(6): 6119-25, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24659449

RESUMO

Glutathione S-transferase (GST), a phase II metabolizing enzyme, plays an important role in the cellar defense system, and its activity may modulate leukemia risk. A large body of evidence has shown the possible relevance of functional polymorphisms of the genes that encode GSTs µ, π, and θ (GSTM1, GSTP1, and GST1, respectively) to the genetic susceptibility of chronic myeloid leukemia (CML). Because of the lack of available conclusive data, we performed a meta-analysis of all relevant available studies to derive a more precise estimation of the relationship. A comprehensive literature search of PubMed and Web of Knowledge electronic databases was conducted to collect relevant studies until December 20, 2013, and the extracted data were statistically analyzed using Review Manager version 5.2. Finally, 16 eligible studies were identified in the literature. The GSTT1 null genotype was associated with an increased risk of CML, as were the double null GSTT1 and GSTM1 genotypes. These findings suggest that heritable GST status influences the risk of developing CML and that more attention should be paid to carriers of these susceptibility genes.


Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Risco
18.
Jpn J Clin Oncol ; 44(11): 1070-81, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25145382

RESUMO

OBJECTIVE: A large body of evidence has shown the possible relevance of polymorphisms of the genes that encode glutathione S-transferase µ, π and θ (GSTM1, GSTP1 and GST1, respectively) to the susceptibility of acute myeloid leukemia, but the exact association still remains uncertain. Therefore, we performed a meta-analysis to derive a more precise estimation of the relationship. METHODS: A comprehensive literature search of PubMed and Web of Knowledge electronic databases was conducted to collect relevant studies until 20 February 2014. References of the retrieved articles were also screened. The extracted data were statistically analyzed, and pooled odds ratios with 95% confidence intervals were calculated to estimate the association strength using Review Manager version 5.2. RESULTS: Twenty-nine studies were included in the meta-analysis. The pooled analyses revealed that the GSTM1-null genotype was associated with an increased risk of acute myeloid leukemia in East Asians (P = 0.01; odds ratio = 1.22; 95% confidence interval = 1.05-1.42), and GSTT1-null genotype in Caucasians (P < 0.0001; odds ratio = 1.48; 95% confidence interval = 1.29-1.69). There was also a predilection towards the female gender for both of these polymorphisms. For GSTP1 Ile105Val polymorphism, no significant association was found under any contrast model. In addition, the presence of the double-null genotypes increased the risk of acute myeloid leukemia in both Caucasians and East Asians. CONCLUSIONS: This meta-analysis suggested that heritable GST status could influence the risk of developing acute myeloid leukemia.


Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Leucemia Mieloide Aguda/genética , Polimorfismo Genético , Povo Asiático/genética , Predisposição Genética para Doença , Genótipo , Humanos , Isoleucina , Razão de Chances , Fatores de Risco , Valina , População Branca/genética
19.
Food Chem ; 441: 138373, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38219365

RESUMO

An autoinducer-2 (AI-2) signaling molecule from Bacillus was synthesized, and its mechanism on the biofilm formation and biocontrol ability of B. amyloliquefaciens was verified in vitro and in vivo. The 16S/ITS amplicon sequencing was used to analyze the effect of B. amyloliquefaciens B4 with or without AI-2 on the microflora of pears during storage. The results showed that B. amyloliquefaciens B4 secreted AI-2, which promoted biofilm formation. Additionally, AI-2 at a concentration of 40 µmol/L enhanced the biocontrol ability of B. amyloliquefaciens B4 on postharvest pear and loquat fruits. Finally, amplicon sequencing demonstrated that the addition of AI-2 increased the abundance of B. amyloliquefaciens B4 in fruit by stimulating the growth and biofilm formation of this bacterium.


Assuntos
Bacillus amyloliquefaciens , Bacillus , Eriobotrya , Pyrus , Frutas/microbiologia
20.
J Cosmet Dermatol ; 23(4): 1452-1464, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38214419

RESUMO

BACKGROUND: The skin condition of women is different at different ages, and skin surface lipids are also different. According to the "7-7 theory" of the Huangdi Neijing, the physiological condition of women changes significantly every 7 years, and women aged 22-28 are in the "4-7" stage as mentioned in the "7-7 theory" of the Huangdi Neijing. Women's skin is in different states at different ages and produces different lipids. OBJECTIVES: To explore the key lipids that contribute to skin differences between women aged 22-28 and 29-35 years, and to explore the relationship with physiological parameters and daily routine. METHODS: Differential lipids were detected and screened between 22-28 year old (group D1) and 29-35 year old (group D2) dry-skinned women using UPLC-Q-TOF-MS and correlated between the two groups with questionnaires and physiological parameters based on basic information, lifestyle habits, work situation, and emotional stress. RESULTS: The results showed that all of the eight major classes of lipids had the highest expression in the D2 group, with the largest differences in glycerophospholipids, glycerol esters, and fatty acids. The BMI value of D2 group was higher than that of D1 group, the skin elasticity index (R2) and brightness index (L, a, ITA values) were lower than that of D1 group, and Cer (d18:0/16:0) was positively correlated with the R2, L, a, and ITA, and LMSP01080056 (N,N-dimethyl-Safingol) was positively correlated with the b-value, the LMSPGP03020013, LMSPGP03020014, LMSP03020024 were significantly negatively correlated with R2. CONCLUSIONS: Cer(d18:0/16:0) is a neurosphingol that inhibits elastase expression. N,N-dimethyl-Safingol readily undergoes oxidation to form yellow-brown solids. The macromolecular structure and excessive carbonyl structure of [LMGP0302] are susceptible to cross-linking and carbonyl stress reactions, which accelerate skin aging and reduce skin elasticity, and thus, they may be key lipids contributing to skin differences between the two age groups.


Assuntos
Lipidômica , Lipídeos , Esfingosina/análogos & derivados , Humanos , Feminino , Adulto Jovem , Adulto , Lipídeos/análise , Ácidos Graxos/metabolismo , Pele/metabolismo
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