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1.
Eur J Pediatr ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771371

RESUMO

The association between breastfeeding and the occurrence of allergic rhinitis (AR) and food allergy (FA) in offspring remains inconclusive. This review aims to comprehensively explore the potential relationships between various patterns and durations of breastfeeding and allergic diseases in offspring. We systematically searched PubMed, EMBASE, Cochrane, WOS databases, and Google Scholar for observational studies published up to March 30, 2023, that investigated the link between breastfeeding and allergies in offspring. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI). Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated employing an appropriate model based on the degree of heterogeneity. A total of 68 studies, encompassing 772,142 children, were ultimately included. The findings indicated that breastfeeding for more than 6 months was associated with a reduced risk of AR (OR = 0.88, 95% CI: 0.79 to 0.98) but posed a risk for FA (OR = 1.69, 95% CI: 1.27 to 2.25). Exclusive breastfeeding exhibited a protective effect against AR (OR = 0.94, 95% CI: 0.90 to 0.97), whereas non-breastfeeding was identified as a risk factor for AR (OR = 1.48; 95% CI: 1.03 to 2.12). No significant association was observed between breastfeeding patterns and FA. CONCLUSION: Breastfeeding for more than 6 months proves to be an effective preventive measure against AR. However, large prospective high-quality studies are needed to investigate the potential risk of FA in children with prolonged breastfeeding. WHAT IS KNOWN: • The impact of breastfeeding on allergic rhinitis and food allergy in offspring is controversial. • Previous meta-analyses fail to prove the effect of breastfeeding on food allergy in offspring of all ages. WHAT IS NEW: • Breastfeeding for more than 6 months proves to be an effective preventive measure against AR. However, it potentially elevates the risk of FA in children. Non-breastfeeding is linked to an increased risk of AR in children, but there is no evidence of an association between breastfeeding patterns and FA in children. • The impact of breastfeeding on allergic rhinitis and food allergy in offspring may vary with the time and pattern of breastfeeding.

2.
Blood ; 136(13): 1520-1534, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32396934

RESUMO

High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the IKAROS (encoded by the IKZF1 gene) tumor suppressor. Here, we report that IKAROS regulates expression of the BCL2L1 gene (encodes the BCL-XL protein) in human B-ALL. Gain-of-function and loss-of-function experiments demonstrate that IKAROS binds to the BCL2L1 promoter, recruits histone deacetylase HDAC1, and represses BCL2L1 expression via chromatin remodeling. In leukemia, IKAROS' function is impaired by oncogenic casein kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces IKAROS binding and recruitment of HDAC1 to the BCL2L1 promoter. This results in a loss of IKAROS-mediated repression of BCL2L1 and increased expression of BCL-XL. Increased expression of BCL-XL and/or CK2, as well as reduced IKAROS expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, increases binding of IKAROS to the BCL2L1 promoter and enhances IKAROS-mediated repression of BCL2L1 in B-ALL. Treatment with CX-4945 increases sensitivity to doxorubicin in B-ALL, and reverses resistance to doxorubicin in multidrug-resistant B-ALL. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia. These data lay the groundwork for clinical testing of a rationally designed, targeted therapy that combines the CK2 inhibitor, CX-4945, with doxorubicin for the treatment of hematopoietic malignancies.


Assuntos
Caseína Quinase II/genética , Resistencia a Medicamentos Antineoplásicos , Regulação Leucêmica da Expressão Gênica , Fator de Transcrição Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína bcl-X/genética , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
3.
Mikrochim Acta ; 189(12): 456, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36416994

RESUMO

In order to improve the selectivity and stability of melamine-formaldehyde (MF) aerogel, it was composited with TiO2 aerogel. A TiO2-MF hybrid aerogel was in situ prepared on the surface of carbon fibers for in-tube solid-phase microextraction (SPME). The extraction performance of TiO2-MF aerogel was regulated by changing the ratio of TiO2 sol and MF sol during the material preparation. Coupled with high-performance liquid chromatography-diode array detection (HPLC-DAD), the extraction tube filled by TiO2-MF aerogel-coated carbon fibers was evaluated with several types of environmental pollutants including polycyclic aromatic hydrocarbons (PAHs), estrogens, and ultraviolet filters. Because of favourable extraction performance of PAHs they were selected as model analytes, and some important influence factors were optimized for satisfactory sensitivity. The detection limits were in the range 0.05-0.10 µg L-1, owing to high enrichment factors (653-1007). The online in-tube SPME-HPLC-DAD method was verified for the determination of trace PAHs in environmental water samples, and acceptable recovery (70-118%) was achieved. The analytical methods also displayed some advantages in comparison with other reports. Moreover, the extraction tube exhibited satisfactory chemical stability.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Microextração em Fase Sólida , Cromatografia Líquida de Alta Pressão , Fibra de Carbono , Formaldeído
4.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4505-4516, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046880

RESUMO

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.


Assuntos
Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas , Influenza Humana , Ácidos Nucleicos , Tosse , Medicamentos de Ervas Chinesas/uso terapêutico , Fadiga , Febre/tratamento farmacológico , Humanos , Influenza Humana/tratamento farmacológico , Metanálise como Assunto , Medicamentos sem Prescrição/uso terapêutico , Ácidos Nucleicos/uso terapêutico , Oseltamivir/uso terapêutico , Ribavirina/uso terapêutico
5.
New Phytol ; 229(3): 1339-1353, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32989748

RESUMO

Root access to bedrock water storage or groundwater is an important trait allowing plant survival in seasonally dry environments. However, the degree of coordination between water uptake depth, leaf-level water-use efficiency (WUEi) and water potential in drought-prone plant communities is not well understood. We conducted a 135-d rainfall exclusion experiment in a subtropical karst ecosystem with thin skeletal soils to evaluate the responses of 11 co-occurring woody species of contrasting life forms and leaf habits to a severe drought during the wet growing season. Marked differences in xylem water isotopic composition during drought revealed distinct ecohydrological niche separation among species. The contrasting behaviour of leaf water potential in coexisting species during drought was largely explained by differences in root access to deeper, temporally stable water sources. Smaller-diameter species with shallower water uptake, more negative water potentials and lower WUEi showed extensive drought-induced canopy defoliation and/or mortality. By contrast, larger-diameter species with deeper water uptake, higher leaf-level WUEi and more isohydric behaviour survived drought with only moderate canopy defoliation. Severe water limitation imposes strong environmental filtering and/or selective pressures resulting in tight coordination between tree diameter, water uptake depth, iso/anisohydric behaviour, WUEi and drought vulnerability in karst plant communities.


Assuntos
Secas , Água , Ecossistema , Folhas de Planta , Árvores
6.
Int J Mol Sci ; 22(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467550

RESUMO

IKAROS, encoded by the IKZF1 gene, is a DNA-binding protein that functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL). Recent studies have identified IKAROS's novel function in the epigenetic regulation of gene expression in T-ALL and uncovered many genes that are likely to be directly regulated by IKAROS. Here, we report the transcriptional regulation of two genes, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) and phosphoinositide kinase, FYVE-type zinc finger containing (PIKFYVE), by IKAROS in T-ALL. PIK3CD encodes the protein p110δ subunit of phosphoinositide 3-kinase (PI3K). The PI3K/AKT pathway is frequently dysregulated in cancers, including T-ALL. IKAROS binds to the promoter regions of PIK3CD and PIKFYVE and reduces their transcription in primary T-ALL. Functional analysis demonstrates that IKAROS functions as a transcriptional repressor of both PIK3CD and PIKFYVE. Protein kinase CK2 (CK2) is a pro-oncogenic kinase that is overexpressed in T-ALL. CK2 phosphorylates IKAROS, impairs IKAROS's DNA-binding ability, and functions as a repressor of PIK3CD and PIKFYVE. CK2 inhibition results in increased IKAROS binding to the promoters of PIK3CD and PIKFYVE and the transcriptional repression of both these genes. Overall, the presented data demonstrate for the first time that in T-ALL, CK2 hyperactivity contributes to PI3K signaling pathway upregulation, at least in part, through impaired IKAROS transcriptional regulation of PIK3CD and PIKFYVE. Targeting CK2 restores IKAROS's regulatory effects on the PI3K oncogenic signaling pathway.


Assuntos
Caseína Quinase II/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Regulação Leucêmica da Expressão Gênica , Fator de Transcrição Ikaros/genética , Fosfatidilinositol 3-Quinases/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Caseína Quinase II/antagonistas & inibidores , Caseína Quinase II/metabolismo , Linhagem Celular Tumoral , Montagem e Desmontagem da Cromatina/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Células HEK293 , Humanos , Fator de Transcrição Ikaros/metabolismo , Naftiridinas/farmacologia , Fenazinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Transdução de Sinais/genética
7.
J Org Chem ; 85(2): 612-621, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31804078

RESUMO

We report the first example of the construction of chiral 2,3-benzodiazepine compounds which are of biologic and pharmaceutical relevance by asymmetric catalysis. Catalyzed by a thiazolium-derived carbene and a palladium-chiral bidentate phosphine complex in sequence, one-pot reaction between 1-(2-(2-nitrovinyl)aryl)allyl esters 1 with azodicarboxylates 2 took place efficiently at ambient temperature to produce 4-nitro-1-vinyl-1H-2,3-benzodiazepine-2,3-dicarboxylates 5 in good to excellent yields with an enantiomeric ratio of up to 95:5.

8.
Int J Mol Sci ; 21(4)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085659

RESUMO

Regulation of oncogenic gene expression by transcription factors that function as tumor suppressors is one of the major mechanisms that regulate leukemogenesis. Understanding this complex process is essential for explaining the pathogenesis of leukemia as well as developing targeted therapies. Here, we provide an overview of the role of Ikaros tumor suppressor and its role in regulation of gene transcription in acute leukemia. Ikaros (IKZF1) is a DNA-binding protein that functions as a master regulator of hematopoiesis and the immune system, as well as a tumor suppressor in acute lymphoblastic leukemia (ALL). Genetic alteration or functional inactivation of Ikaros results in the development of high-risk leukemia. Ikaros binds to the specific consensus binding motif at upstream regulatory elements of its target genes, recruits chromatin-remodeling complexes and activates or represses transcription via chromatin remodeling. Over the last twenty years, a large number of Ikaros target genes have been identified, and the role of Ikaros in the regulation of their expression provided insight into the mechanisms of Ikaros tumor suppressor function in leukemia. Here we summarize the role of Ikaros in the regulation of the expression of the genes whose function is critical for cellular proliferation, development, and progression of acute lymphoblastic leukemia.


Assuntos
Regulação Leucêmica da Expressão Gênica , Genes Supressores de Tumor , Fator de Transcrição Ikaros/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Epigênese Genética/efeitos dos fármacos , Humanos , Transdução de Sinais
9.
Int J Mol Sci ; 21(5)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138279

RESUMO

Ikaros is a DNA-binding protein that regulates gene expression and functions as a tumor suppressor in B-cell acute lymphoblastic leukemia (B-ALL). The full cohort of Ikaros target genes have yet to be identified. Here, we demonstrate that Ikaros directly regulates expression of the small GTPase, Rab20. Using ChIP-seq and qChIP we assessed Ikaros binding and the epigenetic signature at the RAB20 promoter. Expression of Ikaros, CK2, and RAB20 was determined by qRT-PCR. Overexpression of Ikaros was achieved by retroviral transduction, whereas shRNA was used to knockdown Ikaros and CK2. Regulation of transcription from the RAB20 promoter was analyzed by luciferase reporter assay. The results showed that Ikaros binds the RAB20 promoter in B-ALL. Gain-of-function and loss-of-function experiments demonstrated that Ikaros represses RAB20 transcription via chromatin remodeling. Phosphorylation by CK2 kinase reduces Ikaros' affinity toward the RAB20 promoter and abolishes its ability to repress RAB20 transcription. Dephosphorylation by PP1 phosphatase enhances both Ikaros' DNA-binding affinity toward the RAB20 promoter and RAB20 repression. In conclusion, the results demonstrated opposing effects of CK2 and PP1 on expression of Rab20 via control of Ikaros' activity as a transcriptional regulator. A novel regulatory signaling network in B-cell leukemia that involves CK2, PP1, Ikaros, and Rab20 is identified.


Assuntos
Fator de Transcrição Ikaros/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Doença Aguda , Linhagem Celular Tumoral , Humanos , Fator de Transcrição Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteínas rab de Ligação ao GTP/genética
10.
J Org Chem ; 83(16): 8971-8983, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-29894194

RESUMO

We report in this paper the N-heterocyclic carbene/transition metal and N-heterocyclic carbene/base cascade catalysis in the reaction of o-alkynylbenzaldehydes with N-acylimines, demonstrating the example of reaction pathways steered by catalysts. Under the catalysis of a thiazole carbene/Et3N followed by Cu(OAc)2 in acetonitrile at ambient temperature, o-alkynylbenzaldehydes underwent reaction with N-acylimines that were generated in situ from N-((aryl)(tosyl)methyl)amides to produce a pair of Z- and E-2-amido-3-benzylidene-1-indanones in 47-92% total yields. The reaction of the same substrates in the presence of a thiazole carbene and Cs2CO3, on the other hand, afforded (1 E,3 Z)-1-amidobenzylidene-3-benzylidene-1,3-dihydroisobenzofurans in 54-89% yields.

11.
J Org Chem ; 83(4): 1913-1923, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29319303

RESUMO

The cascade catalysis involving N-heterocyclic carbene (NHC) and palladium/ligand was demonstrated. In the presence of a triazolium salt, palladium catalyst, and base, the reaction of 3-(2-formylphenoxy)propenoates and allylic esters proceeded efficiently under mild conditions to afford 2-allylbenzofuran-3-one-2-acetates in moderated to good yields. An asymmetric cascade catalysis was achieved when (R)-BINAP was employed as a chiral ligand, producing enantiomerically enriched 2,2-disubstitiuted benzofuran-3-one derivatives with an ee up to 81%.

12.
J Biol Chem ; 291(8): 4004-18, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26655717

RESUMO

Impaired function of the Ikaros (IKZF1) protein is associated with the development of high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL). The mechanisms of Ikaros tumor suppressor activity in leukemia are unknown. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. Here, we report that Ikaros represses transcription of the histone H3K4 demethylase, JARID1B (KDM5B). Transcriptional repression of JARID1B is associated with increased global levels of H3K4 trimethylation. Ikaros-mediated repression of JARID1B is dependent on the activity of the histone deacetylase, HDAC1, which binds to the upstream regulatory element of JARID1B in complex with Ikaros. In leukemia, JARID1B is overexpressed, and its inhibition results in cellular growth arrest. Ikaros-mediated repression of JARID1B in leukemia is impaired by pro-oncogenic casein kinase 2 (CK2). Inhibition of CK2 results in increased binding of the Ikaros-HDAC1 complex to the promoter of JARID1B, with increased formation of trimethylated histone H3 lysine 27 and decreased histone H3 Lys-9 acetylation. In cases of high-risk B-ALL that carry deletion of one Ikaros (IKZF1) allele, targeted inhibition of CK2 restores Ikaros binding to the JARID1B promoter and repression of JARID1B. In summary, the presented data suggest a mechanism through which Ikaros and HDAC1 regulate the epigenetic signature in leukemia: via regulation of JARID1B transcription. The presented data identify JARID1B as a novel therapeutic target in B-ALL and provide a rationale for the use of CK2 inhibitors in the treatment of high-risk B-ALL.


Assuntos
Caseína Quinase II/metabolismo , Epigênese Genética , Regulação Enzimológica da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Histona Desacetilase 1/metabolismo , Fator de Transcrição Ikaros/metabolismo , Histona Desmetilases com o Domínio Jumonji/biossíntese , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/biossíntese , Proteínas Repressoras/biossíntese , Transcrição Gênica , Caseína Quinase II/genética , Histona Desacetilase 1/genética , Humanos , Fator de Transcrição Ikaros/genética , Histona Desmetilases com o Domínio Jumonji/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Proteínas Repressoras/genética , Células U937
13.
Blood ; 126(15): 1813-22, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26219304

RESUMO

Ikaros (IKZF1) is a tumor suppressor that binds DNA and regulates expression of its target genes. The mechanism of Ikaros activity as a tumor suppressor and the regulation of Ikaros function in leukemia are unknown. Here, we demonstrate that Ikaros controls cellular proliferation by repressing expression of genes that promote cell cycle progression and the phosphatidylinositol-3 kinase (PI3K) pathway. We show that Ikaros function is impaired by the pro-oncogenic casein kinase II (CK2), and that CK2 is overexpressed in leukemia. CK2 inhibition restores Ikaros function as transcriptional repressor of cell cycle and PI3K pathway genes, resulting in an antileukemia effect. In high-risk leukemia where one IKZF1 allele has been deleted, CK2 inhibition restores the transcriptional repressor function of the remaining wild-type IKZF1 allele. CK2 inhibition demonstrated a potent therapeutic effect in a panel of patient-derived primary high-risk B-cell acute lymphoblastic leukemia xenografts as indicated by prolonged survival and a reduction of leukemia burden. We demonstrate the efficacy of a novel therapeutic approach for high-risk leukemia: restoration of Ikaros tumor suppressor activity via inhibition of CK2. These results provide a rationale for the use of CK2 inhibitors in clinical trials for high-risk leukemia, including cases with deletion of one IKZF1 allele.


Assuntos
Caseína Quinase II/antagonistas & inibidores , Genes Supressores de Tumor , Fator de Transcrição Ikaros/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Animais , Apoptose/efeitos dos fármacos , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , Proliferação de Células/efeitos dos fármacos , Imunoprecipitação da Cromatina , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Fator de Transcrição Ikaros/genética , Camundongos , Camundongos Endogâmicos NOD , Fosfatidilinositol 3-Quinases , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Org Chem ; 81(23): 11871-11881, 2016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27934452

RESUMO

The chiral triazole carbene and Ti(OPr-i)4 cocatalyzed reaction between α,ß-unsaturated aldehydes and 2-(aroylvinyl)benzaldehydes was systematically studied. A divergence in reaction pathways was observed under different reaction conditions. In benzene solvent and at ambient temperature, the reaction produced 4,5-dihydro-1,4-methanobenzo[c]oxepin-3-ones, the bridged caprolactones, as the major products in moderate yields with excellent enantioselectivity. The same reaction in dichloroethane and at 50 °C, however, gave 2,8-dihydrocyclopenta[a]indenes as the major products in most cases. The application of the method developed was demonstrated by the transformation of the bridged lactone products into enantiopure 4-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acids.

15.
Stem Cells ; 32(8): 2278-89, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24740910

RESUMO

Erythroid differentiation-associated gene (EDAG) has been considered to be a transcriptional regulator that controls hematopoietic cell differentiation, proliferation, and apoptosis. The role of EDAG in erythroid differentiation of primary erythroid progenitor cells and in vivo remains unknown. In this study, we found that EDAG is highly expressed in CMPs and MEPs and upregulated during the erythroid differentiation of CD34(+) cells following erythropoietin (EPO) treatment. Overexpression of EDAG induced erythroid differentiation of CD34(+) cells in vitro and in vivo using immunodeficient mice. Conversely, EDAG knockdown reduced erythroid differentiation in EPO-treated CD34(+) cells. Detailed mechanistic analysis suggested that EDAG forms complex with GATA1 and p300 and increases GATA1 acetylation and transcriptional activity by facilitating the interaction between GATA1 and p300. EDAG deletion mutants lacking the binding domain with GATA1 or p300 failed to enhance erythroid differentiation, suggesting that EDAG regulates erythroid differentiation partly through forming EDAG/GATA1/p300 complex. In the presence of the specific inhibitor of p300 acetyltransferase activity, C646, EDAG was unable to accelerate erythroid differentiation, indicating an involvement of p300 acetyltransferase activity in EDAG-induced erythroid differentiation. ChIP-PCR experiments confirmed that GATA1 and EDAG co-occupy GATA1-targeted genes in primary erythroid cells and in vivo. ChIP-seq was further performed to examine the global occupancy of EDAG during erythroid differentiation and a total of 7,133 enrichment peaks corresponding to 3,847 genes were identified. Merging EDAG ChIP-Seq and GATA1 ChIP-Seq datasets revealed that 782 genes overlapped. Microarray analysis suggested that EDAG knockdown selectively inhibits GATA1-activated target genes. These data provide novel insights into EDAG in regulation of erythroid differentiation.


Assuntos
Diferenciação Celular/fisiologia , Proteína p300 Associada a E1A/metabolismo , Fator de Transcrição GATA1/metabolismo , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Proteínas Nucleares/metabolismo , Acetilação , Animais , Western Blotting , Separação Celular , Células Eritroides/citologia , Células Eritroides/metabolismo , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/metabolismo , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Análise de Sequência com Séries de Oligonucleotídeos , Transcriptoma
16.
Mitochondrial DNA B Resour ; 9(1): 195-199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282978

RESUMO

Meconopsis bella Prain 1894 (M. bella) is a rare herb within the family Papaveraceae of which unique and gorgeous purple flowers are blooming in the flowering phase. In this study, we reported the complete chloroplast (cp) genome of M. bella, which was mainly distributed on the Qinghai-Tibet plateau. The complete chloroplast genome sequence of M. bella was 153,073 bp in size and was characterized by a typical quadripartite structure consisting of a large single-copy (LSC) region of 83,562 bp, a small single-copy (SSC) region of 178,33 bp and two identical inverted repeats (IR) regions of 25,839 bp. The genome contained 133 genes, including 88 protein-encoding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. Phylogenetic analysis based on the maximum-likelihood (ML) method showed that M. bella was closely related to M. paniculate and M. pinnatifolia within the genus Meconopsis.

17.
Anal Chim Acta ; 1292: 342258, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38309855

RESUMO

BACKGROUND: Because of the advantages of good selectivity, high sensitivity, and fast analysis, high performance liquid chromatography (HPLC) has become one of the modern analytical techniques in wide application range, such as biological analysis, environmental detection, pharmaceutical and food inspection, agriculture and other fields. The stationary phase greatly decides the chromatographic separation performance, so the development of novel stationary phase is most important for HPLC. RESULTS: Pyridyl conjugated microporous polymers (P-CMP) with one to four layers were modified on the surface of amino silica to obtain a novel core-shell material (SiO2@P-CMP) by the layer-by-layer assembly strategy and Chichibabin reaction. The relationship between the structure of SiO2@P-CMP and chromatographic performance was carefully investigated, and the retention mechanism was revealed. The interactions including π-π stacking, hydrophobic effect and hydrogen bond gradually enhanced with the increase of P-CMP layers on the silica surface. Compared with C18 column, SiO2@P-CMP columns displayed better separation selectivity for polycyclic aromatic hydrocarbons (PAHs). According to the relative retention values (α), the separation performance of SiO2@P-CMP columns (α = 1.144-1.884) for PAH isomers and other analytes was obviously better than that of C18 column (α = 0.998-1.487). Furthermore, the SiO2@P-CMP column with four layers was selected to separate different types of analytes (eight PAHs, four bisphenols, four estrogens and nine phthalates), and the peak order of analytes was different from that on the C18 column due to the influence of hydrogen-bonding and π-π interactions. The relative standard deviations (n = 10) of retention time and peak area on SiO2@P-CMP column were between 0.28 % and 1.98 %. SIGNIFICANCE AND NOVELTY: Pyridyl conjugated microporous polymer was introduced as the stationary phase for the first time in HPLC. The proposed column displayed better separation characteristics compared to Zorbax SB-C18 column. It provided a new idea for the separation of small molecules and the development of chromatographic packing or extraction material.

18.
Food Chem ; 445: 138706, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367557

RESUMO

The accurate detection of analytes in honey is affected by the complex substrates, making it crucial to employ an effective sample preparation technique. In this work, an imidazolium ionic liquid was functionalized to the silica surface by a click reaction for solid-phase extraction (SPE) column, and in situ anion-exchange process was performed with different organic anions (dodecyl sulfonate, dodecyl benzene sulfonate, and naphthalene sulfonate). These SPE columns were evaluated through extracting the estrogens. The naphthalene sulfonate-based SPE column displayed the best extraction ability among these, and it was combined with high-performance liquid chromatography-diode array detection to establish an online enrichment and analysis system. Under the optimal test conditions, an online analytical method was developed, with high enrichment factors (1872-4744), wide linear ranges (0.0033-1.50, 0.0165-1.50, and 0.0330-1.50 µg g-1), and low detection limits (0.001-0.010 µg g-1). The method successfully determined several estrogens in some honey samples, and achieved satisfactory recovery results.


Assuntos
Mel , Líquidos Iônicos , Dióxido de Silício , Estrogênios/análise , Mel/análise , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão , Ânions , Naftalenos
19.
Clin Chim Acta ; 556: 117843, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387830

RESUMO

BACKGROUND: It is difficult to distinguish between acute myocardial infarction (AMI) and unstable angina (UA) due to their similar clinical features. In recent years, studies have shown that microbiomes have great potential in distinguishing diseases. The purpose of this study is to describe the composition of serum microbiome in the AMI and UA by 16S rDNA sequencing. METHODS: Based on the high-throughput detection platform and 16S rDNA amplification sequencing technology, this study detected the blood microbial composition of 55 patients with AMI and 62 patients with UA. Alpha diversity and Beta diversity analysis were used to compare the differences in microbial composition and bacterial colony structure between AMI and UA groups. We perform PCoA (Principal Co-ordinates Analysis) based on Unweighted Unifrac distance. In addition, various statistical methods were employed to examine the significance of differences in microbial composition and genus between the two groups. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was employed to predict KEGG (Kyoto Encyclopedia of Genes and Genomes) function from 16S sequencing data. Random forest was applied to identify biomarkers and construct the diagnostic model. Subsequently, the stability of the model was verified by 10-fold cross and the diagnostic effectiveness was evaluated through ROC (Receiver Operating Characteristic). RESULTS: In this study, we found that alpha diversity index of serum microbiome in AMI group was significantly higher than in UA group. T-test analysis demonstrated that the UA group presented a higher abundance of Ralstonia, Faecalibaculum and Gammaproteobacteria, while Bacteroides, Sphingomonas, Faecalibaculum, Haemophilus, Serratia, Bifidobacterium and Chloroplast were more abundant in the AMI group. The LefSe (LDA Effect Size) analysis showed that the Gammaproteobacteria, Proteobacteria, Ralstonia pickettli, Ralstonia, Burkholderiaceae and Burkholderiales were enriched in UA group, and Bacteroidales, Bacteroidia, Bacteroidota, Clostridia and Firmicutes were more abundant in the AMI group. Ten bacterial diagnostic models were constructed in the random forest. The area under the curve (AUC) in the training set was 88.01%, and the AUC value in the test set was 95.04%. CONCLUSION: In this study, the composition of blood microorganisms in the groups of patients with AMI and UA has been analyzed, providing novel insights for understanding the pathogenesis of AMI; Blood microbiome may serve as novel diagnostic biomarkers of AMI.


Assuntos
Microbiota , Infarto do Miocárdio , Humanos , Filogenia , Infarto do Miocárdio/diagnóstico , Microbiota/genética , Biomarcadores , DNA Ribossômico
20.
Eur J Pharmacol ; 963: 176271, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38113965

RESUMO

Respiratory syncytial virus (RSV) pneumonia is the main cause of acute bronchiolitis in infants. Luteolin-7-O-glucoside (LUT-7G) is a natural flavonoid, which exists in a variety of plants and has the potential to treat viral pneumonia. We established RSV pneumonia mouse models and RSV-infected cell models. Clodronate liposomes were used to deplete macrophages. We used HE staining and immunohistochemistry to determine inflammatory damage and virus replication. We detected the expression levels of inflammatory factors and IFN-ß through qPCR and ELISA. JC-1 kit was used for detecting the cell mitochondrial Membrane potential (MMP). ROS, SOD, and MDA kits were used for detecting intracellular oxidative stress damage. Metabolites of TCA in lung tissue and serum of mice were detected by GC-MS. Pharmacodynamic studies have shown that intervention with LUT-7G can alleviate lung tissue damage caused by RSV infection, inhibit RSV replication, and downregulate TNF-α, IL-1ß, and IL-6 mRNA expression. LUT-7G upregulated the IFN-ß content and the expression of IFN-ß, ISG15, and OAS1 mRNA. In vitro, LUT-7G inhibited RSV-induced cell death, reversed the RSV-induced decrease of MMP and decreased intracellular oxidative stress. Target metabonomics showed that RSV infection upregulated the levels of glycolysis and TCA metabolites in lung tissue and serum, while LUT-7G could improve the disorder of glucose metabolism. The results indicate that LUT-7G can promote the release of IFN-ß in the lung, alleviate inflammatory damage, and inhibit RSV replication during RSV infection. These effects may be achieved by protecting the mitochondrial function of alveolar macrophages and correcting the disorder of glucose metabolism.


Assuntos
Interferon beta , Luteolina , Mitocôndrias , Infecções por Vírus Respiratório Sincicial , Animais , Humanos , Camundongos , Glucose/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pneumonia/metabolismo , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/metabolismo , RNA Mensageiro , Luteolina/farmacologia , Interferon beta/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
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