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1.
ISME J ; 18(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38691444

ABSTRACT

Plant-associated microbiomes play important roles in plant health and productivity. However, despite fruits being directly linked to plant productivity, little is known about the microbiomes of fruits and their potential association with fruit health. Here, by integrating 16S rRNA gene, ITS high-throughput sequencing data, and microbiological culturable approaches, we reported that roots and fruits (pods) of peanut, a typical plant that bears fruits underground, recruit different bacterial and fungal communities independently of cropping conditions and that the incidence of pod disease under monocropping conditions is attributed to the depletion of Bacillus genus and enrichment of Aspergillus genus in geocarposphere. On this basis, we constructed a synthetic community (SynCom) consisting of three Bacillus strains from geocarposphere soil under rotation conditions with high culturable abundance. Comparative transcriptome, microbiome profiling, and plant phytohormone signaling analysis reveal that the SynCom exhibited more effective Aspergillus growth inhibition and pod disease control than individual strain, which was underpinned by a combination of molecular mechanisms related to fungal cell proliferation interference, mycotoxins biosynthesis impairment, and jasmonic acid-mediated plant immunity activation. Overall, our results reveal the filter effect of plant organs on the microbiome and that depletion of key protective microbial community promotes the fruit disease incidence.


Subject(s)
Arachis , Fruit , Microbiota , Plant Diseases , Plant Roots , RNA, Ribosomal, 16S , Soil Microbiology , Fruit/microbiology , Plant Diseases/microbiology , Plant Diseases/prevention & control , RNA, Ribosomal, 16S/genetics , Plant Roots/microbiology , Arachis/microbiology , Aspergillus/genetics , Aspergillus/isolation & purification , Bacillus/genetics , Bacillus/isolation & purification , Plant Growth Regulators/metabolism , Fungi/genetics , Fungi/classification , Fungi/isolation & purification , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification
2.
Chem Sci ; 15(21): 8156-8162, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38817557

ABSTRACT

The first straightforward strategy for the synthesis of 1,4-dicarbonyl Z-alkenes has been developed via an electrochemical cross-coupling reaction of sulfoxonium ylides and alkynes with water. The metal-free protocol showed an easy-to-handle nature, good functional group tolerance, and high Z-stereoselectivity, which is rare in previous cases. The proposed reaction mechanism was convincingly established by carrying out a series of control experiments, cyclic voltammetry experiments, and density functional theory (DFT) studies.

3.
Soc Sci Med ; 345: 116680, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38394947

ABSTRACT

Previous studies have reported the relationship between educational attainment and attention deficit hyperactivity disorder (ADHD). However, the mechanism of this relationship remains unknown. It is well known that educational attainment correlates with income. Therefore, based on summary data from a genome-wide association study we used two-step Mendelian randomization (MR) to explore the role of income between education and ADHD. The inverse variance weighted (IVW) method was used in our analysis. The IVW results suggested that educational attainment and income were protective factors against ADHD. Educational attainment affects ADHD through income [ADHD: Beta = -0.68, 95% confidence interval (CI) = -0.87, -0.49; female: Beta = -0.87, 95% CI = -1.28, -0.47; male: Beta = -1.01, 95% CI = -1.34, -0.68; childhood: Beta = -0.52, 95% CI = -0.74, -0.30; late-diagnosed: Beta = -0.78, 95% CI = -1.11, -0.47; persistent: Beta = -0.82, 95% CI = -1.33, -0.31]. Income also affected ADHD through educational attainment [female: Beta = -1.08, 95% CI = -1.35, -0.83; male: Beta = -1.16, 95% CI = -1.57, -0.77; persistent: Beta = -1.48, 95% CI = -2.09, -0.94]. In the final analysis, data with heterogeneity were analyzed using IVW random effects results. The mechanism is that income will mediate the relationship between educational attainment and ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Humans , Male , Female , Child , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/genetics , Mediation Analysis , Genome-Wide Association Study , Mendelian Randomization Analysis/methods , Educational Status
4.
Chem Biol Drug Des ; 103(1): e14364, 2024 01.
Article in English | MEDLINE | ID: mdl-37806947

ABSTRACT

With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug-tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 µM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 µM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta-position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure-activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action.


Subject(s)
Candida auris , Candida , Sulfonylurea Compounds , Humans , Antifungal Agents/pharmacology , Structure-Activity Relationship , Microbial Sensitivity Tests
5.
Org Biomol Chem ; 21(43): 8646-8650, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37870475

ABSTRACT

A straightforward electrochemical protocol for efficient hydrogenation of unsaturated CC bonds has been reported in an undivided cell. A series of versatile 1,4-diketones are smoothly generated under metal-free and external-reductant-free electrolytic conditions. Moreover, the tolerance of various functional groups and decagram-scale experiments have shown the practicability and potential applications of this methodology. Moreover, a range of heterocyclic compounds were easily prepared through follow-up procedures of 1,4-diketones.

6.
J Am Chem Soc ; 145(42): 23121-23130, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37844009

ABSTRACT

Upconversion (UC) is a fascinating anti-Stokes-like optical process with promising applications in diverse fields. However, known UC mechanisms are mainly based on direct energy transfer between metal ions, which constrains the designability and tunability of the structures and properties. Here, we synthesize two types of Ln8L12-type (Ln for lanthanide ion; L for organic ligand L1 or L2R/S) lanthanide-organic complexes with assembly induced excited-multimer states. The Yb8(L2R/S)12 assembly exhibits upconverted multimer green fluorescence under 980 nm excitation through a cooperative sensitization process. Furthermore, upconverted red emission from Eu3+ on the heterometallic (Yb/Eu)8L12 assemblies is also realized via excited-multimer mediated energy relay. Our findings demonstrate a new strategy for designing UC materials, which is crucial for exploiting photofunctions of multicomponent lanthanide-organic complexes.

8.
Front Immunol ; 14: 1152881, 2023.
Article in English | MEDLINE | ID: mdl-37153557

ABSTRACT

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.


Subject(s)
Heart Failure , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Hypertension, Pulmonary/metabolism , Familial Primary Pulmonary Hypertension/metabolism , Macrophages/metabolism , Heart Failure/metabolism
9.
BMC Genomics ; 24(1): 273, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37208602

ABSTRACT

BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.


Subject(s)
Bacillus subtilis , Killer Cells, Natural , Animals , Mice , Killer Cells, Natural/metabolism , T-Lymphocytes/metabolism , Interferon-gamma , Phagocytosis
10.
Pest Manag Sci ; 79(5): 1885-1896, 2023 May.
Article in English | MEDLINE | ID: mdl-36700288

ABSTRACT

BACKGROUND: In order to design compounds with fresh molecular skeleton to break through the limitation of available agrochemicals, a series of 36 novel selenenyl sulfide compounds were chemically synthesized, and their biological activities were fully evaluated against tobacco mosaic virus (TMV), 14 plant pathogenic fungi, three insect species and plant acetohydroxyacid synthase (AHAS). RESULTS: All the target compounds were characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR, selenium-77 (77 Se)-NMR, and high-resolution mass spectrometry (HRMS). The crystal structure of 10j indicated that the Se-S bond was successfully constructed. Compounds 10d, 10h, 10s, 10u, 10aa, 10ac, 10ae, 10ag, and 10ai exhibited 40%, 43%, 39%, 41%, 47%, 46%, 47%, 42%, and 39% anti-TMV activities at 500 mg L-1 , better than that of ribavirin. The median effective concentration (EC50 ) against Sclerotinia sclerotiorum of 10ac was 6.69 mg L-1 and EC50 values against Physalospora piricola and Pyricularia grisea of 10z were 12.25 mg L-1 and 15.27 mg L-1 , respectively, superior to the corresponding values of chlorothalonil. Compounds 10c and 10v demonstrated 100% larvicidal activity against Culex pipiens pallens at 5 mg L-1 , while 10a displayed 100% insecticidal activity against Mythimna separata at 200 mg L-1 . Compounds 10c, 10j, and 10o showed > 60% inhibitions against plant AHAS at 10 µmol L-1 . From the quantum calculation, highest occupied molecular orbital (HOMO) was considered as a factor that affects the anti-TMV activity. CONCLUSION: The preliminary results suggested that more efforts should be devoted to exploring the selenenyl sulfides for the discovery of new leads of antiviral agent, fungicide, insecticide or AHAS inhibitors as potential agrochemicals for crop protection. © 2023 Society of Chemical Industry.


Subject(s)
Fungicides, Industrial , Insecticides , Moths , Tobacco Mosaic Virus , Animals , Structure-Activity Relationship , Fungicides, Industrial/chemistry , Antiviral Agents , Insecticides/chemistry , Sulfides/pharmacology , Molecular Structure , Drug Design
11.
J Plast Surg Hand Surg ; 57(1-6): 122-128, 2023.
Article in English | MEDLINE | ID: mdl-34964674

ABSTRACT

Proliferation is an important characteristic of life, and many signaling pathways participate in this complicated process. The MAPK/Erk pathway is a classic pathway in cell proliferation. In this study, expression levels of key factors in the MAPK/Erk pathway were measured to assess the proliferation level among normal skin, physiological scar, and keloid tissue. Thirty patients were selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January 2019 to December 2020. Histological appearance and fiber tissue content were observed by Hematoxylin and eosin staining and Masson staining. Expression levels of key factors in the MAPK/Erk pathway (ATF2, c-Jun, c-Myc, p38 and STAT1) and relative proteins (HIF-1α and PCNA) in tissues were detected by immunohistochemistry and analyzed as the percentage of positively stained cells in both the tissue epidermis and dermis. Western blot was used for quantitative analysis of the above factors. In results, keloid tissue showed a significantly higher fiber and less cell content. In the immunohistochemical result, higher expression of key factors was observed in the epidermis than in the dermal layer, and the expression of all factors was increased remarkably in keloid tissue. In western blot analysis, all factors (except STAT1) showed higher expression in keloid tissue. In our former research, keloid showed similar apoptosis level as physiological scar and normal skin. On combining our former conclusion and results in this study, an imbalance condition between the high proliferation level and normal apoptosis level may lead to the growth characteristics of keloid.


Subject(s)
Keloid , Humans , Keloid/pathology , Cell Proliferation , Apoptosis , Fibroblasts/pathology
12.
J Plast Surg Hand Surg ; 57(1-6): 324-329, 2023.
Article in English | MEDLINE | ID: mdl-35522455

ABSTRACT

Photodynamic therapy (PDT) is a new therapy for treating cancer with less toxicity, high selectivity, good cooperativity, and repetitive usability. However, keloid treatment by PDT is mainly focused on clinical appearance, and few studies have been conducted on the mechanisms of PDT. In this study, key factors of the classical mitochondrial apoptosis signaling pathway were measured to assess the effect of a new PDT photosensitizer (p1). A specific inhibitor of caspase-8 (Z-IETD-FMK) was also used to verify the possible mechanisms. Twelve samples were obtained from 12 patients (six with keloids and six without) selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January to December 2020. After cell culture, fibroblasts were divided into 13 groups. The morphology of fibroblasts in each group was observed by microscopy. Cell activity was measured by cell counting kit-8, and cell apoptotic morphology was observed by TUNEL staining. The reactive oxygen species (ROS) relative value was measured by a ROS test kit. The expression levels of key mitochondrial factors (caspase-3, caspase-8, cytochrome-c, Bax, and Bcl-2) were assessed by western blot, and mRNA expression of caspase-3 and caspase-8 was measured by RT-qPCR. We showed that p1 had a satisfactory proapoptotic effect on keloid fibroblasts by increasing the expression of ROS, caspase-3, caspase-8, and cytochrome-c, and decreasing the Bcl-2/Bax ratio; however, this effect was partially inhibited by Z-IETD-FMK, indicating that caspase-8 may be one of the p1's targets to achieve the proapoptotic effect.


Subject(s)
Keloid , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/metabolism , Photosensitizing Agents/therapeutic use , Caspase 3/metabolism , Caspase 3/pharmacology , Caspase 3/therapeutic use , Keloid/drug therapy , Keloid/pathology , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/pharmacology , Reactive Oxygen Species/therapeutic use , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacology , Caspase 8/metabolism , Caspase 8/pharmacology , Caspase 8/therapeutic use , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/pharmacology , Proto-Oncogene Proteins c-bcl-2/therapeutic use , Fibroblasts/pathology , Cytochromes/metabolism , Cytochromes/pharmacology , Cytochromes/therapeutic use
13.
ACS Omega ; 7(29): 24942-24950, 2022 Jul 26.
Article in English | MEDLINE | ID: mdl-35910152

ABSTRACT

The abiotic reaction products of polycyclic aromatic hydrocarbons (PAHs) with hydroxyl radicals (•OH) and nitrate radicals (•NO3) are nitro-, oxygen-, and hydroxyl-containing PAHs (NPAHs, OPAHs, and OHPAHs). Four methods of the highest occupied molecular orbital (HOMO), Fukui function (FF), dual descriptor (DD), and population of π electrons (PP-π) are selected to predict the chemical reactivity of PAHs attacked by •OH and •NO3 in this study. The predicted •OH-initiated and •NO3-initiated transformation products are compared with the main PAH transformation products (PAH-TPs) observed in the laboratory. The results indicate that PP-π and DD approaches fail to predict the transformation products of fused PAHs containing five-membered rings. By predicting the PAH-TPs of 13-14 out of the 15 parent PAHs accurately, HOMO and FF methods were shown to be suitable for predicting the transformation products formed from the abiotic reactions of fused PAHs with •OH and •NO3.

14.
Cardiovasc Ther ; 2022: 9615674, 2022.
Article in English | MEDLINE | ID: mdl-35692375

ABSTRACT

Purpose: L-carnitine (LC) is considered to have good therapeutic potential for myocardial infarction (MI), but its mechanism has not been clarified. The aim of the study is to elucidate the cardioprotective effects of LC in mice following MI and related mechanisms. Methods: ICR mice were treated with LC for 2 weeks after induction of MI with ligation of left anterior descending artery. Electrocardiographic (ECG) recording and echocardiography were used to evaluate cardiac function. H&E staining, TTC staining, and Masson staining were performed for morphological analysis and cardiac fibrosis. ELISA and immunofluorescence were utilized to detect biomarkers and inflammatory mediators. The key proteins in the Bax/Bcl-2 signaling pathway were also examined by Western blot. Results: Both echocardiography and histological measurement showed an improvement in cardiac function and morphology. Biomarkers such as LDH, NT-proBNP, cTnT, and AST, as well as the inflammatory cytokines IL-1ß, IL-6, and TNF-α, were decreased in plasma of mice receiving LC treatment after myocardial injury. In addition, the expression of α-SMA as well as the key proteins in the Bax/Bcl-2 signaling pathway in cardiac myocardium were much lower in mice with LC treatment compared to those without after MI. Conclusions: Our data suggest that LC can effectively ameliorate left ventricular (LV) remodeling after MI, and its beneficial effects on myocardial function and remodeling may be attributable at least in part to anti-inflammatory and inhibition of the Bax/Bcl-2 apoptotic signaling pathway.


Subject(s)
Myocardial Infarction , Ventricular Remodeling , Animals , Apoptosis , Carnitine/metabolism , Carnitine/pharmacology , Carnitine/therapeutic use , Disease Models, Animal , Mice , Mice, Inbred ICR , Myocardium/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction , bcl-2-Associated X Protein/metabolism
15.
Zhongguo Zhong Yao Za Zhi ; 47(4): 938-950, 2022 Feb.
Article in Chinese | MEDLINE | ID: mdl-35285193

ABSTRACT

Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 µm) with water-acetonitrile as mobile phase, a column temperature of 30 ℃, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 µL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.


Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Benchmarking , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Tandem Mass Spectrometry/methods
16.
Rev Assoc Med Bras (1992) ; 67(4): 555-560, 2021 Apr.
Article in English | MEDLINE | ID: mdl-34495060

ABSTRACT

OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3ß, and ß-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3ß, and ß-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.


Subject(s)
Vascular Endothelial Growth Factor A , Cell Proliferation , Cells, Cultured , Glycogen Synthase Kinase 3 beta , Human Umbilical Vein Endothelial Cells , Humans
17.
J Agric Food Chem ; 69(30): 8415-8427, 2021 Aug 04.
Article in English | MEDLINE | ID: mdl-34283603

ABSTRACT

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with ortho-alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.5 g ha-1, 6-11 exhibited more potent herbicidal activity against barnyard grass (Echinochloa crus-galli) and crab grass (Digitaria sanguinalis) than commercial acetohydroxyacid synthase (AHAS; EC 2.2.1.6) inhibitors triasulfuron, penoxsulam, and nicosulfuron at both pre-emergence and postemergence conditions. 6-11 was safe for peanut for postemergence application at this ultralow dosage, suggesting that it could be considered a potential herbicide candidate for peanut fields. Although 6-11 and triasulfuron share similar chemical structures and have close Ki values for plant AHAS, a significant difference has been observed between their LUMO maps from DFT calculations, which might be a possible factor that leads to their different behaviors toward monocotyledon weed species.


Subject(s)
Herbicides , Alcohols , Digitaria , Herbicides/pharmacology , Structure-Activity Relationship , Sulfonylurea Compounds/pharmacology
18.
Front Pharmacol ; 12: 636975, 2021.
Article in English | MEDLINE | ID: mdl-33995039

ABSTRACT

High-dose methotrexate (HD-MTX) can be highly effective as well as extremely toxic. Many drug molecules can bind to plasma proteins to different extents in vivo, whereas only the free drug can reach the site of action to exert a pharmacological effect and cause toxicity. However, free MTX concentrations in plasma have not been reported. Traditional analyses of free drugs are both cumbersome and inaccurate. We collected 92 plasma samples from 52 children diagnosed with ALL or NHL or other lymphomas that were treated with HD-MTX. The hollow fiber centrifugal ultrafiltration (HFCF-UF) was used to prepare plasma samples for analysis of the free MTX concentration. Protein precipitation was employed to measure the total MTX concentration. The HFCF-UF is a simple method involving a step of ordinary centrifugation; the validation parameters for the methodological results were satisfactory and fell within the acceptance criteria. A linearity coefficient r 2 of 0.910 was obtained for the correlation between the free and total MTX plasma concentrations in 92 plasma samples. However, the free and total MTX concentrations was only weakly correlated in 16 clinical plasma specimens with total MTX concentrations >2 µmol L-1 (r 2 = 0.760). Both the free and total MTX concentrations at 42 h were negatively correlated with the creatinine clearance (CCr) level (P = 0.023, r = -0.236 for total MTX and P = 0.020, r = -0.241for free MTX, respectively). The free MTX concentration could not be accurately estimated from the total MTX concentration for patients with high MTX levels which are conditions under which toxic reactions are more likely to occur. High plasma MTX levels could become a predictor of the occurrence of MTX nephrotoxicity to draw people's attention. The proposed HFCF-UF method is a simple and accurate way to evaluate efficacy and toxicity in clinical therapeutic drug monitoring.

19.
Rev. Assoc. Med. Bras. (1992) ; 67(4): 555-560, Apr. 2021. graf
Article in English | LILACS | ID: biblio-1340629

ABSTRACT

SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.


Subject(s)
Humans , Vascular Endothelial Growth Factor A , Cells, Cultured , Cell Proliferation , Human Umbilical Vein Endothelial Cells , Glycogen Synthase Kinase 3 beta
20.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1333-1338, 2021 Mar.
Article in Chinese | MEDLINE | ID: mdl-33787129

ABSTRACT

Astragali Radix is one of traditional Chinese medicines with effects in invigorating Qi for consolidating superficies, inducing diuresis to alleviate edema, promoting pus discharge and tissue regeneration. In recent years, the traditional Chinese medicine fermentation technology has received extensive attentions due to its high efficiency and safety. The pharmacological functions of traditional Chinese medicines could be further enhanced after microbial fermentation, which has a broad development prospects. In this paper, we summarized relevant literatures of Astragali Radix fermentation in such aspects as fermentation strains, fermentation forms, process optimization, active ingredients and pharmacological effects, in the expectation of providing a reference for development and utilization of Astragali Radix.


Subject(s)
Astragalus Plant , Drugs, Chinese Herbal , Fermentation , Medicine, Chinese Traditional , Plant Roots
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