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1.
Plant Cell Environ ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148214

RESUMO

Chilling stress is a major environmental factor that significantly reduces crop production. To adapt to chilling stress, plants activate a series of cellular responses and accumulate an array of metabolites, particularly proline. Here, we report that the transcription factor SlWRKY51 increases proline contents in tomato (Solanum lycopersicum) under chilling stress. SlWRKY51 expression is induced under chilling stress. Knockdown or knockout of SlWRKY51 led to chilling-sensitive phenotypes, with lower photosynthetic capacity and more reactive oxygen species (ROS) accumulation than the wild type (WT). The proline contents were significantly reduced in SlWRKY51 knockdown and knockout lines under chilling stress, perhaps explaining the phenotypes of these lines. D-1-pyrroline-5-carboxylate synthetase (P5CS), which catalyses the rate-limiting step of proline biosynthesis, is encoded by two closely related P5CS genes (P5CS1 and P5CS2). We demonstrate that SlWRKY51 directly activates the expression of P5CS1 under chilling stress. In addition, the VQ (a class of plant-specific proteins containing the conserved motif FxxhVQxhTG) family member SlVQ10 physically interacts with SlWRKY51 to enhance its activation of P5CS1. Our study reveals that the chilling-induced transcription factor SlWRKY51 enhances chilling tolerance in tomato by promoting proline accumulation.

2.
Opt Express ; 32(10): 16712-16721, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858870

RESUMO

With the development of laser technology, nonlinear optics plays a crucial role in frequency conversion. However, the generation of second harmonics in nonlinear optical crystals is generally subject to rigorous phase-matching conditions that hinder the performance of broadband tunability. It is believed that introducing disorders in nonlinear optical materials is helpful to overcome this obstacle. In this work, we have prepared a nonlinear microcrystal-doped glass (NMG) composite material, allowing for tunable and polarization-independent nonlinear conversion from visible to near-infrared. The linear dependence of SHG intensity versus sample thickness indicated the facilitation of random quasi-phase matching by using the NMG. Our results provide a more stable and promising platform for disordered nonlinear photonic materials and suggest the possibility of more efficient nonlinear conversions using the NMG composite glass fibers in future.

3.
Plant Dis ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300849

RESUMO

Wheat stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is an important airborne disease worldwide. Pst inoculum strength in southern Henan in winter or early spring is important for spring epidemic in the main autumn-sown wheat-growing regions of China. However, there is limited knowledge about the source and time of initial infection on winter wheat in southern Henan. The first occurrence of wheat stripe rust in southern Henan was recorded annually from 2011-2022, from which we used the backward trajectory approach to infer the likely source of Pst inoculum responsible for the initial disease occurrence. The results suggested that the Pst inoculum responsible for initial rust established in the winter in southern Henan originated from the Gansu Pst oversummering area in China, whereas it originated from the adjacent winter Pst sporulation regions in southern Shaanxi and northwestern Hubei if Pst symptoms were first observed in early spring in southern Henan. Another possible Pst source is southern Hubei where Pst can also sporulate in the winter. Thus, early Pst development in winter in the main wheat production in China (Henan) is likely to be caused by Pst inoculum spread from the oversummering inocula or Pst epidemics in autumn seedlings in Gansu.

4.
Actas Esp Psiquiatr ; 52(4): 445-452, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39129691

RESUMO

BACKGROUND: Lung cancer is a significant health concern, and is often accompanied by comorbid depression, leading to worsened prognosis and decreased quality of life for patients. This study aimed to investigate the potential influence of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and comorbid depression. METHODS: A retroactive analysis of clinical information from patients with squamous cell lung cancer and comorbid depression admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from June 2022 to June 2023 was conducted. The patients were classified into two groups on the basis of different dietary care approaches: the Routine Dietary Group and the Omega-3 Fatty Acids Group. Baseline characteristics, pulmonary function tests, dietary intake, depression scoring, and quality of life scores were compared between the two groups. RESULTS: 103 patients in total were included, with 51 in the Routine Dietary Group and 52 in the Omega-3 Fatty Acids Group. The Omega-3 Fatty Acids Group exhibited significantly higher ingestion of Omega-3 fatty acids in comparison with the Routine Dietary Group (3.15 ± 0.64 g/day vs. 2.93 ± 0.28 g/day, p = 0.022). Despite similar baseline pulmonary function tests, patients in the Omega-3 Fatty Acids Group showed significantly higher scores in physical (70.17 ± 4.81 vs. 68.18 ± 5.03, p = 0.043) and emotional (71.29 ± 4.58 vs. 69.38 ± 4.25, p = 0.030) functioning, as well as lower scores in insomnia (27.41 ± 4.51 vs. 29.34 ± 4.21, p = 0.027) and constipation (7.34 ± 1.66 vs. 8.43 ± 3.36, p = 0.040). CONCLUSION: The study provided insights into the potential impact of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and complicating depression, suggesting that dietary interventions emphasizing Omega-3 fatty acids may be conducive to improving physical and emotional functioning, as well as symptom management, in this patient population.


Assuntos
Depressão , Ácidos Graxos Ômega-3 , Neoplasias Pulmonares , Qualidade de Vida , Humanos , Ácidos Graxos Ômega-3/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/dietoterapia , Neoplasias Pulmonares/complicações , Estudos Retrospectivos , Depressão/dietoterapia , Depressão/epidemiologia , Idoso , Dieta , Carcinoma de Células Escamosas/dietoterapia
5.
Molecules ; 27(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35684477

RESUMO

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH3O-, CH3-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds CU-19 and CU-21 reduced the level of NO, TNF-α, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin.


Assuntos
Microglia , NF-kappa B , Animais , Anti-Inflamatórios/farmacologia , Compostos de Bifenilo/farmacologia , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Ratos
6.
J Hepatol ; 75(2): 400-413, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33746084

RESUMO

BACKGROUND & AIMS: Cholestatic liver diseases comprise a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury. Regulation of bile acid (BA) synthesis and homeostasis is a promising strategy for the treatment of cholestatic liver disease. Limb expression 1-like protein (LIX1L) plays an important role in post-transcriptional gene regulation, yet its role in cholestatic liver injury remains unclear. METHODS: LIX1L expression was studied in patients with primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC), and 3 murine models of cholestasis (bile duct ligation [BDL], Mdr2 knockout [Mdr2-/-], and cholic acid [CA] feeding). Lix1l knockout mice were employed to investigate the function of LIX1L in cholestatic liver diseases. Chromatin immunoprecipitation assays were performed to determine whether Egr-1 bound to the Lix1l promoter. MiRNA expression profiling was analyzed by microarray. An adeno-associated virus (AAV)-mediated hepatic delivery system was used to identify the function of miR-191-3p in vivo. RESULTS: LIX1L expression was increased in the livers of patients with PSC and PBC, and in the 3 murine models, as well as in BA-stimulated primary mouse hepatocytes. BA-induced Lix1l upregulation was dependent on Egr-1, which served as a transcriptional activator. LIX1L deficiency attenuated cholestatic liver injury in BDL and Mdr2-/- mice. MiR-191-3p was the most reduced miRNA in livers of WT-BDL mice, while it was restored in Lix1l-/--BDL mice. MiR-191-3p targets and downregulates Lrh-1, thereby inhibiting Cyp7a1 and Cyp8b1 expression. AAV-mediated hepatic delivery of miR-191-3p significantly attenuated cholestatic liver injury in Mdr2-/- mice. CONCLUSIONS: LIX1L deficiency alleviates cholestatic liver injury by inhibiting BA synthesis. LIX1L functions as a nexus linking BA/Egr-1 and miR-191-3p/LRH-1 signaling. LIX1L and miR-191-3p may be promising targets for the treatment of BA-associated hepatobiliary diseases. LAY SUMMARY: Bile acid homeostasis can be impaired in cholestatic liver diseases. Our study identified a novel mechanism of positive feedback regulation in cholestasis. LIX1L and miR-191-3p represent potential therapeutic targets for cholestatic liver diseases.


Assuntos
Ácidos e Sais Biliares/metabolismo , Icterícia Obstrutiva/etiologia , Proteínas de Ligação a RNA/metabolismo , Animais , Modelos Animais de Doenças , Icterícia Obstrutiva/genética , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Biliar/complicações , Camundongos , Proteínas de Ligação a RNA/genética
7.
J Nat Prod ; 84(4): 1135-1148, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33788569

RESUMO

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (1-10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A-J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.


Assuntos
Hypericum/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Floroglucinol/farmacologia , Linhagem Celular , China , Frutas/química , Humanos , Estrutura Molecular , Floroglucinol/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Prenilação
8.
Bioorg Chem ; 111: 104910, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33894432

RESUMO

A series of compounds were designed and synthesized based on the compound 11i bearing phenylpyrazole scaffold with histone deacetylase 6 (HDAC6) inhibitory activity. Most of the compounds showed considerable inhibitory activity against HDAC6 and compound A16 with good inhibitory activity was found therein. We further found that A16 had an inhibitory effect on inflammatory mediators (NO, TNF-α, IL-6) involved in inflammatory response and neuroendocrine regulation. In addition, A16 has a certain neuroprotective effect on PC12 cells injured by hydrogen peroxide. Acute toxicity assay showed that the LD50 of A16 was 274.47 mg/kg in mouse model. Furthermore, A16 displayed good stability properties in microsomes and plasma.


Assuntos
Desenho de Fármacos , Desacetilase 6 de Histona/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Indazóis/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Desacetilase 6 de Histona/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Indazóis/síntese química , Indazóis/química , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Propriedades de Superfície
9.
Biotechnol Lett ; 40(9-10): 1335-1341, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29876794

RESUMO

OBJECTIVE: To enhance the production of phenolic compounds during barley germination using chitooligosaccharide as an elicitor to improve the antioxidant capacity of malt. RESULTS: When used as an elicitor for barley germination, chitooligosaccharide with a molecular weight of 3 kDa, added at 10 mg/kg barley kernels during the first steeping cycle, led to the maximum production of phenolic compounds. Compared with the control with no chitooligosaccharide added to the steeping water, the total phenolic content was increased by 54.8%. Increases in the total phenolic content of the barley malt occurred when chitooligosaccharide was applied during the first or both the first and the second steeping cycles. Thus the antioxidant capacity of barley malt was increased significantly by adding chitooligosaccharide during the steeping process. CONCLUSION: Applying chitooligosaccharides during the steeping process increased the content of phenolic compounds thus improving the antioxidant capacity of the barley malt.


Assuntos
Antioxidantes/metabolismo , Quitina/análogos & derivados , Germinação , Hordeum/crescimento & desenvolvimento , Hordeum/metabolismo , Fenóis/metabolismo , Compostos Fitoquímicos/metabolismo , Quitina/metabolismo , Quitosana , Oligossacarídeos
10.
Pediatr Res ; 77(5): 625-32, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25675425

RESUMO

BACKGROUND: Intrauterine growth restriction (IUGR) followed by postnatal accelerated growth (CG-IUGR) is associated with long-term adverse metabolic consequences, and an involvement of epigenetic dysregulation has been implicated. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key orchestrator in energy homeostasis. We hypothesized that CG-IUGR programed an insulin-resistant phenotype through the alteration in DNA methylation and transcriptional activity of PGC-1α. METHODS: A CG-IUGR rat model was adopted using maternal gestational nutritional restriction followed by infantile overnutrition achieved by reducing the litter size. The DNA methylation was determined by pyrosequencing. The mRNA expression and mitochondrial content were assessed by real-time PCR. The insulin-signaling protein expression was evaluated by western blotting. RESULTS: Compared with controls, the CG-IUGR rats showed an increase in the DNA methylation of specific CpG sites in PGC-1α, and a decrease in the transcriptional activity of PGC-1α, mitochondrial content, protein level of PI3K and phosphorylated-Akt2 in liver and muscle tissues. The methylation of specific CpG sites in PGC-1α was positively correlated with fasting insulin concentration. CONCLUSION: IUGR followed by infantile overnutrition programs an insulin-resistant phenotype, possibly through the alteration in DNA methylation and transcriptional activity of PGC-1α. The genetic and epigenetic modifications of PGC-1α provide a potential mechanism linking early-life nutrition insult to long-term metabolic disease susceptibilities.


Assuntos
Ciências da Nutrição Animal , Metilação de DNA , Epigênese Genética , Retardo do Crescimento Fetal/fisiopatologia , Resistência à Insulina , Insulina/metabolismo , Fatores de Transcrição/metabolismo , Animais , Ilhas de CpG , DNA Mitocondrial/metabolismo , Modelos Animais de Doenças , Ácidos Graxos/química , Homeostase , Fígado/metabolismo , Masculino , Músculos/metabolismo , Oxigênio/química , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fenótipo , Fosforilação , Ratos , Análise de Sequência de DNA , Temperatura , Triglicerídeos/metabolismo
11.
Molecules ; 19(5): 6671-82, 2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24858099

RESUMO

Two series of amino-modified derivatives of (S)-perillyl alcohol were designed and synthesized using (S)-perillaldehyde as the starting material. These derivatives showed increased antiproliferative activity in human lung cancer A549 cells, human melanoma A375-S2 cells and human fibrosarcoma HT-1080 cells comparing with that of (S)-perillyl alcohol. Among these derivatives, compounds VI5 and VI7 were the most potent agents, with the IC50s below 100 µM. It was demonstrated that the antiproliferative effect of VI5 was mediated through the induction of apoptosis in A549 cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Monoterpenos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Técnicas de Química Sintética , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Monoterpenos/farmacologia , Relação Estrutura-Atividade
12.
Foods ; 13(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38790873

RESUMO

Red yeast rice dietary supplements have been proven to ameliorate hyperglycemia, but the mechanism was unclear. In this work, ankaflavin (AK) and monascin (MS), as typical pigments derived from red yeast rice, were found to exert noteworthy inhibitory ability against α-glucosidase, with an IC50 of 126.5 ± 2.5 and 302.6 ± 2.5 µM, respectively, compared with acarbose (IC50 = 341.3 ± 13.6 µM). They also exhibited mixed-type inhibition of α-glucosidase in vitro and caused fluorescence quenching through the static-quenching process. Molecular-docking studies indicated that AK and MS bind to amino acid residues outside the catalytic center, which induces structural changes in the enzyme, thus influencing its catalytic activity. The anti-glycation ability of Monascus-fermented products was evaluated, and they exhibited a high inhibition rate of 87.1% in fluorescent advanced glycation end-product formation at a concentration of 0.2 mg mL-1, while aminoguanidine showed a rate of 75.7% at the same concentration. These results will be significant in broadening the application scope of Monascus pigments, especially AK and MS, in treating type 2 diabetes.

13.
Biomolecules ; 14(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38540689

RESUMO

Stress is known to induce a reduction in adult hippocampal neurogenesis (AHN) and anxiety-like behaviors. Glucocorticoids (GCs) are secreted in response to stress, and the hippocampus possesses the greatest levels of GC receptors, highlighting the potential of GCs in mediating stress-induced hippocampal alterations and behavior deficits. Herein, RNA-sequencing (RNA-seq) analysis of the hippocampus following corticosterone (CORT) exposure revealed the central regulatory role of the p21 (Cdkna1a) gene, which exhibited interactions with oxidative stress-related differentially expressed genes (DEGs), suggesting a potential link between p21 and oxidative stress-related pathways. Remarkably, p21-overexpression in the hippocampal dentate gyrus partially recapitulated CORT-induced phenotypes, including reactive oxygen species (ROS) accumulation, diminished AHN, dendritic atrophy, and the onset of anxiety-like behaviors. Significantly, inhibiting ROS exhibited a partial rescue of anxiety-like behaviors and hippocampal alterations induced by p21-overexpression, as well as those induced by CORT, underscoring the therapeutic potential of targeting ROS or p21 in the hippocampus as a promising avenue for mitigating anxiety disorders provoked by chronic stress.


Assuntos
Corticosterona , Hipocampo , Corticosterona/farmacologia , Corticosterona/metabolismo , Espécies Reativas de Oxigênio , Hipocampo/metabolismo , Depressão/tratamento farmacológico , Neurogênese/fisiologia
14.
Environ Pollut ; 344: 123394, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266699

RESUMO

Microplastics (MPs) are ubiquitously present in source water and undergo ultraviolet (UV) aging in aquatic environments before entering drinking water treatment plants. The presence of MPs in drinking water can impact the formation of halogenated disinfection byproducts (DBPs) during chlorine disinfection, yet the exact effect of MPs on DBP formation remain unclear. In this study, we conducted an investigation into the influence of non-aged and UV-aged MPs on halogenated DBP formation in drinking water and unveiled the underlying mechanisms. In comparison to source water samples devoid of MPs, the total organic halogen concentration was reduced by 19%-43% and 4%-13% in the drinking water samples containing non-aged and aged MPs, respectively. The differing effects on halogenated DBP formation can be attributed to the alternation in physical and chemical characteristics of MPs following UV aging. Aged MPs exhibited larger surface area with signs of wear and tear, heightened hydrophilicity, surface oxidation, increased oxygen-containing functional groups and dechlorination during the UV aging process. Both non-aged and aged MPs possess the capability to adsorb natural organic matter, leading to a reduction in the concentration of DBP precursors in the source water. However, the release of organic compounds from aged MPs outweighed the adsorption of organics. Furthermore, as a result of the surface activation of MPs through the UV aging process, the aged MPs themselves can also serve as DBP precursors. Consequently, the presence of halogenated DBP precursors in source water increased, contributing to a higher level of DBP formation compared to source water containing non-aged MPs. Overall, this study illuminates the intricate relationship among MPs, UV aging, and DBP formation in drinking water. It highlights the potential risks posed by aged MPs in influencing DBP formation and offers valuable insights for optimizing water treatment processes.


Assuntos
Desinfetantes , Água Potável , Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Microplásticos , Plásticos , Poluentes Químicos da Água/análise , Cloro/química
15.
Stem Cell Res Ther ; 15(1): 107, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637896

RESUMO

BACKGROUND: The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process. METHODS: A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation. RESULTS: We found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination. CONCLUSIONS: For the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN.


Assuntos
Serotonina , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Diferenciação Celular/genética , Perfilação da Expressão Gênica , Neurônios , Genes Reporter
16.
Artigo em Inglês | MEDLINE | ID: mdl-37844406

RESUMO

Magnolol and honokiol have been reported to exhibit anti-cancer activity. However, few studies are in relation to the interaction of magnolol/honokiol with vascular endothelial growth factor 2 (VEGFR2). In this study, a membrane chromatography method based on VEGFR2 was established for the interaction characteristic analysis between drug and receptor. The selectivity, repeatability and stability of the chromatographic model were evaluated using drugs acting on different receptors. The affinity between VEGFR2 and magnolol/honokiol was verified by cell membrane chromatography. The binding sites of magnolol/honokiol and VEGFR2 were analyzed by zonal elution. Especially, the dissociation equilibrium constants (Kd) of magnolol/honokiol and VEGFR2 were measured by zonal elution and stepwise frontal analysis respectively. In addition, the actions of magnolol/honokiol on VEGFR2 were analyzed by stepwise frontal analysis at different temperatures. The results showed that the binding sites of magnolol and honokiol on VEGFR2 were different from sorafenib, indicating that magnolol and honokiol could be used as competitive agents for self-competitive displacement experiment. The Kd values (order of magnitude) of magnolol/honokiol with VEGFR2 measured by stepwise frontal analysis were consistent with the zonal elution results. Honokiol binds VEGFR2 with higher affinity than magnolol. The main forces that stabilize the interactions of honokiol with VEGFR2 are hydrogen bonds and van der Waal's forces, and the main force of magnolol is electrostatic forces. These discoveries could assist in the prediction of drug activity and understanding for the underlying mechanism.


Assuntos
Lignanas , Fator A de Crescimento do Endotélio Vascular , Compostos de Bifenilo/química , Cromatografia , Membrana Celular
17.
Data Sci Eng ; 8(2): 196-219, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197366

RESUMO

The success of blockchain technology in cryptocurrencies reveals its potential in the data management field. Recently, there is a trend in the database community to integrate blockchains and traditional databases to obtain security, efficiency, and privacy from the two distinctive but related systems. In this survey, we discuss the use of blockchain technology in the data management field and focus on the fusion system of blockchains and databases. We first classify existing blockchain-related data management technologies by their locations on the blockchain-database spectrum. Based on the taxonomy, we discuss three types of fusion systems and analyze their design spaces and trade-offs. Then, by further investigating the typical systems and techniques of each type of fusion system and comparing the solutions, we provide insights of each fusion model. Finally, we outline the unsolved challenges and promising directions in this field and believe that fusion systems will take a more important role in data management tasks. We hope this survey can help both academia and industry to better understand the advantages and limitations of blockchain-related data management systems and develop fusion systems that meet various requirements in practice.

18.
Adv Sci (Weinh) ; 10(32): e2303884, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37679064

RESUMO

Directed differentiation of serotonin neurons (SNs) from human pluripotent stem cells (hPSCs) provides a valuable tool for uncovering the mechanism of human SN development and the associated neuropsychiatric disorders. Previous studies report that FOXA2 is expressed by serotonergic progenitors (SNPs) and functioned as a serotonergic fate determinant in mouse. However, in the routine differentiation experiments, it is accidentally found that less SNs and more non-neuronal cells are obtained from SNP stage with higher percentage of FOXA2-positive cells. This phenomenon prompted them to question the role of FOXA2 as an intrinsic fate determinant for human SN differentiation. Herein, by direct differentiation of engineered hPSCs into SNs, it is found that the SNs are not derived from FOXA2-lineage cells; FOXA2-knockout hPSCs can still differentiate into mature and functional SNs with typical serotonergic identity; FOXA2 overexpression suppresses the SN differentiation, indicating that FOXA2 is not intrinsically required for human SN differentiation. Furthermore, repressing FOXA2 expression by retinoic acid (RA) and dynamically modulating Sonic Hedgehog (SHH) signaling pathway promotes human SN differentiation. This study uncovers the role of FOXA2 in human SN development and improves the differentiation efficiency of hPSCs into SNs by repressing FOXA2 expression.


Assuntos
Células-Tronco Pluripotentes , Serotonina , Humanos , Camundongos , Animais , Serotonina/metabolismo , Proteínas Hedgehog/metabolismo , Neurônios/metabolismo , Diferenciação Celular/fisiologia , Células-Tronco Pluripotentes/metabolismo , Fator 3-beta Nuclear de Hepatócito/genética , Fator 3-beta Nuclear de Hepatócito/metabolismo
19.
Plant Physiol Biochem ; 204: 108090, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37847973

RESUMO

Blue honeysuckle (Lonicera caerulea L.) is an emerging commercial fruit in the world, has been known for its multiple anthocyanins in the berries, cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and it makes up 76-92% of the total anthocyanins content, with high antioxidant capacity, and widely used in food products. In this review, recent studies related to anthocyanins in blue honeysuckle were sorted out, including the current status of research on anthocyanins in blue honeysuckle berries, especially C3G, qualitative and quantitative analysis of anthocyanins in berries, extraction and purification methods of anthocyanins from blue honeysuckle, in addition, biological effects of blue honeysuckle, and recommended utilization. Blue honeysuckle contains polyphenols, flavonoids, anthocyanins, minerals, and multiple bioactive compounds, it has been extensively reported to have significant antioxidant, cardioprotective, anti-inflammatory, neuroprotective, anticancer, and anti-diabetic functions, and has been used in a variety of food products as raw materials.


Assuntos
Antocianinas , Lonicera , Antocianinas/análise , Antioxidantes/farmacologia , Flavonoides/análise , Polifenóis/análise , Frutas/química , Extratos Vegetais
20.
Stem Cells Int ; 2022: 5283615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345626

RESUMO

Rcor2, the corepressor 2 of REST, a transcriptional repressor, is predominantly expressed in embryonic stem cells (ESCs) and plays a major role in regulating ESC pluripotency and neurogenesis. The function of Rcor2 in development of other germ layers is yet unclear. We utilized a Rcor2-/- mouse embryonic stem cell (mESC) line to investigate the role of Rcor2 in mESC differentiation. Rcor2-/- mESC shows reduced proliferation and severely compromised capacity to differentiate to all three germ layers. In contrast, Rcor2 knockout promotes primordial germ cells (PGCs) specific gene expression and possibly PGC formation. Mechanistically, we revealed that Rcor2 inhibits expression of genes required for PGC development, such as Dppa3 and Dazl, by associating to their promoters and enhancing local suppressive H3K9me3 modifications. Our results suggest that Rcor2 plays an important role in somatic cell fate determination by suppressing PGC differentiation through regulating epigenetic modifications of PGC specific genes.

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