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1.
PLoS Pathog ; 19(6): e1011011, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37276223

RESUMO

Isoprothiolane (IPT) resistance has emerged in Magnaporthe oryzae, due to the long-term usage of IPT to control rice blast in China, yet the mechanisms of the resistance remain largely unknown. Through IPT adaptation on PDA medium, we obtained a variety of IPT-resistant mutants. Based on their EC50 values to IPT, the resistant mutants were mainly divided into three distinct categories, i.e., low resistance (LR, 6.5 ≤ EC50 < 13.0 µg/mL), moderate resistance 1 (MR-1, 13.0 ≤ EC50 < 25.0 µg/mL), and moderate resistance 2 (MR-2, 25.0 ≤ EC50 < 35.0 µg/mL). Molecular analysis of MoIRR (Magnaporthe oryzae isoprothiolane resistance related) gene demonstrated that it was associated only with the moderate resistance in MR-2 mutants, indicating that other mechanisms were associated with resistance in LR and MR-1 mutants. In this study, we mainly focused on the characterization of low resistance to IPT in M. oryzae. Mycelial growth and conidial germination were significantly reduced, indicating fitness penalties in LR mutants. Based on the differences of whole genome sequences between parental isolate and LR mutants, we identified a conserved MoVelB gene, encoding the velvet family transcription factor, and genetic transformation of wild type isolate verified that MoVelB gene was associated with the low resistance. Based on molecular analysis, we further demonstrated that the velvet family proteins VelB and VeA were indispensable for IPT toxicity and the deformation of the VelB-VeA-LaeA complex played a vital role for the low IPT-resistance in M. oryzae, most likely through the down-regulation of the secondary metabolism-related genes or CYP450 genes to reduce the toxicity of IPT.


Assuntos
Ascomicetos , Magnaporthe , Oryza , Magnaporthe/genética , Tiofenos , Oryza/genética , Doenças das Plantas
2.
FASEB J ; 38(13): e23663, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38958986

RESUMO

This study delves into the unexplored realm of castration-resistant prostate cancer (CRPC) by investigating the role of TRIM28 and its intricate molecular mechanisms using high-throughput single-cell transcriptome sequencing and advanced bioinformatics analysis. Our comprehensive examination unveiled dynamic TRIM28 expression changes, particularly in immune cells such as macrophages and CD8+ T cells within CRPC. Correlation analyses with TCGA data highlighted the connection between TRIM28 and immune checkpoint expression and emphasized its pivotal influence on the quantity and functionality of immune cells. Using TRIM28 knockout mouse models, we identified differentially expressed genes and enriched pathways, unraveling the potential regulatory involvement of TRIM28 in the cGAS-STING pathway. In vitro, experiments further illuminated that TRIM28 knockout in prostate cancer cells induced a notable anti-tumor immune effect by inhibiting M2 macrophage polarization and enhancing CD8+ T cell activity. This impactful discovery was validated in an in situ transplant tumor model, where TRIM28 knockout exhibited a deceleration in tumor growth, reduced proportions of M2 macrophages, and enhanced infiltration of CD8+ T cells. In summary, this study elucidates the hitherto unknown anti-tumor immune role of TRIM28 in CRPC and unravels its potential regulatory mechanism via the cGAS-STING signaling pathway. These findings provide novel insights into the immune landscape of CRPC, offering promising directions for developing innovative therapeutic strategies.


Assuntos
Linfócitos T CD8-Positivos , Proteínas de Membrana , Neoplasias de Próstata Resistentes à Castração , Proteína 28 com Motivo Tripartido , Animais , Humanos , Masculino , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Macrófagos/metabolismo , Macrófagos/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/imunologia , Neoplasias de Próstata Resistentes à Castração/patologia , Transdução de Sinais , Proteína 28 com Motivo Tripartido/metabolismo , Proteína 28 com Motivo Tripartido/genética
3.
Environ Res ; 248: 118253, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38278507

RESUMO

A weak electric field (WEF, 2 mA cm-2) was employed to promote Fe(III)/Fe(II) cycle on goethite-impregnated activated carbon (FeOOH@AC) filled in a continuous-flow column for enhanced Cr(VI) elimination from water. Surficial analysis and Cr species distribution showed that α-FeOOH of 0.2-1 µm was successfully synthesized and evenly loaded onto AC. Electron transfer from WEF to α-FeOOH was facilitated with AC as electron shuttles, thereby boosting Fe(III) reduction in the α-FeOOH. The generated Fe(II) reduced Cr(VI) and the resultant Cr(III) subsequently precipitated with OH- and Fe(III) to form Cr(OH)3 and (CrχFe1-χ)(OH)3. Therefore, the WEF-FeOOH@AC column exhibited a much lower Cr(VI) migration rate of 0.0018 cm PV-1 in comparison with 0.0037 cm PV-1 of the FeOOH@AC column, equal to 104 % higher Cr(VI) elimination capacity and 90 % longer column service life-span. Additionally, under different Cr(VI) loadings by varying either seepage velocities or influent Cr(VI) concentrations, the WEF-FeOOH@AC column maintained 1.0-1.5 folds higher Cr(VI) elimination and 0.9-1.4 folds longer longevity than those of the FeOOH@AC column owing to the interaction between FeOOH@AC and WEF. Our research demonstrated that WEF-FeOOH@AC was a potential method to promote Cr(VI) elimination from water and offer an effective strategy to facilitate Fe(III)/Fe(II) cycle in iron oxides.


Assuntos
Compostos Férricos , Compostos de Ferro , Minerais , Poluentes Químicos da Água , Água , Carvão Vegetal , Oxirredução , Cromo/análise , Poluentes Químicos da Água/análise , Compostos Ferrosos
4.
J Environ Manage ; 362: 121327, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38824892

RESUMO

In this study, nanoscale cupric oxide-decorated activated carbon (nCuO@AC) was synthesized by impregnation-calcination and employed to assist the decomposition of H2O2 for effective sterilization with Escherichia coli as target bacteria. Characteristic technologies demonstrated that copper oxide particles of 50-100 nm were uniformly distributed on AC surface. Owing to electron transfer from hydroxyl and aldehyde to CuO on AC, surface-bonded Cu(II) was partially reduced to Cu(I) in the nCuO matrix. The resultant Cu(I) expedited the decomposition of H2O2 and converted it into ·OH radicals which were identified by quenching experiment and electron paramagnetic resonance test. Due to oxidation attack of generated ·OH, the nCuO@AC-H2O2 system achieved a much higher inactivation rate of 6.0 log within 30 min as compared to those of 2.1 and 1.3 log in the nCuO@AC and nCuO-H2O2 systems. It also exhibited excellent pH adaptability and high inactivation efficiency under neutral conditions. After four cycles, the nCuO@AC-H2O2 system could still inactivate 5.5 log bacteria, indicating excellent stability and reusability of nCuO@AC. Spent nCuO@AC could be regenerated by eluting surficial copper oxides with hydrochloric acid, and re-coating nCuO particles through impregnation-calcination with a regeneration rate of 96.6%. Our results demonstrated that nCuO@AC was an efficient and prospective catalyst to assist the decomposition of H2O2 for effective inactivation of bacteria in water.


Assuntos
Carvão Vegetal , Cobre , Escherichia coli , Peróxido de Hidrogênio , Escherichia coli/efeitos dos fármacos , Peróxido de Hidrogênio/química , Cobre/química , Carvão Vegetal/química , Carbono/química , Oxirredução
5.
Environ Res ; 236(Pt 2): 116812, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37536558

RESUMO

BACKGROUND: Although numerous studies have examined the effect of prenatal per- and polyfluoroalkyl substances (PFAS) exposure on neurodevelopment in children, findings have been inconsistent. OBJECTIVE: To better understand the effects of PFAS exposure during pregnancy on offspring neurodevelopment, we conducted a systematic review of prenatal exposure to different types of PFAS and neurodevelopment in children. METHODS: A comprehensive search was conducted in the PubMed, Web of Science, and EMBASE electronic databases up to March 2023. Only birth cohort studies that report a specific association between PFAS exposure during pregnancy and neurodevelopment were included in this review. RESULTS: 31 birth cohort studies that met the inclusion criteria were qualitatively integrated. Among these, 14 studies investigated the impact of PFAS exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. Additionally, 4 studies explored the influence of PFAS on children's comprehensive development. CONCLUSION: Prenatal PFAS exposure was associated with poor neurodevelopment in children, including psychomotor development, externalizing behavior, and comprehensive development. However, conclusive evidence regarding its effects on other neurological outcomes remains limited. In addition, sex-specific effects on social behavior and sleep problems were identified.

6.
Plant Cell Rep ; 42(3): 561-574, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36609767

RESUMO

KEY MESSAGE: IiSVP of Isatis indigotica was cloned and its expression pattern was analyzed. Ectopic expression of IiSVP in Arabidopsis could delay the flowering time and reduce the size of the floral organs. SVP (SHORT VEGETATIVE PHASE) can negatively regulate the flowering time of Arabidopsis. In the present work, the cDNA of IiSVP, an orthologous gene of AtSVP in I. indigotica, was cloned. IiSVP was highly expressed in rosette leaves, inflorescences and petals, but weakly expressed in sepals, pistils and young silicles. The results of subcellular localization showed that IiSVP was localized in nucleus. Bioinformatics analysis indicated that this protein was a MADS-box transcription factor. Constitutive expression of IiSVP in Arabidopsis thaliana resulted in decrease of the number of petals and stamens, and curly sepals were formed. In IiSVP transgenic Arabidopsis plants, obvious phenotypic variations in flowers could be observed, especially the size of the floral organs. In comparison with the wild-type plants, the size of petals, stamens and pistil in IiSVP transgenic Arabidopsis plants was decreased significantly. In some transgenic plants, the petals were wrapped by the sepals. Yeast two-hybrid experiments showed that IiSVP could form higher-order complexes with other MADS proteins, including IiSEP1, IiSEP3, IiAP1 and IiSEP4, but could not interact with IiSEP2. In this work, it was proved that the flowering process and the floral development in Arabidopsis could be affected by IiSVP from I. indigotica Fortune.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Isatis , Arabidopsis/metabolismo , Isatis/genética , Isatis/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Proteínas de Plantas/metabolismo , Flores , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Proteínas de Arabidopsis/genética
7.
Acta Biochim Biophys Sin (Shanghai) ; 55(4): 587-600, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37092860

RESUMO

Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its antitumor role remains to be elucidated. The aim of this study is to explore the mechanisms underlying the tumor suppressive activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 eliminates colorectal cancer (CRC) cells by activating gasdermin D (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in turn promotes NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively inhibits the proliferation of CRC cells in vitro and in nude mouse models. Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing great anticancer potential.


Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Animais , Camundongos , Piroptose , Fator 2 Relacionado a NF-E2/genética , Proteína Supressora de Tumor p53 , Caspase 1 , Glutationa , Camundongos Nus , Neoplasias Colorretais/tratamento farmacológico , Fator de Transcrição STAT3
8.
Int J Med Sci ; 19(5): 796-812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693739

RESUMO

Renal cancer incidence has been increasing across the world, clear cell renal cell carcinoma (ccRCC) represents the major subtype of renal cancer. The proteasome is involved in onset, metabolism and survival of tumor and has been recognized as a therapeutic target for various malignancies, while the role of ß subunits of proteasome, PSMB gene family, in ccRCC has not been fully unveiled. Herein we investigated the expression and the prognostic role of PSMBs in ccRCC by analyzing a series of databases, including ONCOMINE, UALCAN, cBioPortal, STRING, GEPIA, GO and KEGG. Over-expressions of PSMB1/2/4/7/8/9/10 mRNA were found in ccRCC tissues compared to normal tissues, transcriptional levels of PSMB2/3/4/6/8/9/10 were significantly positively associated with patients' individual cancer stages and grades. Similar or higher levels of proteins encoded by PSMB1/2/3/7/8/9/10 were observed in tumor tissues compared to normal renal tissues. Further, high mRNA levels of PSMB1/2/3/4/6/10 were correlated with shorter overall survival in univariate analysis. Taken together, the results of our analysis implied that overexpression of PSMB1/2/3/4/6/8/9/10 were indicative of worse prognosis of ccRCC. However, further researches were required to validate our findings.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Biologia Computacional/métodos , Humanos , Neoplasias Renais/patologia , Prognóstico , Complexo de Endopeptidases do Proteassoma/genética , RNA Mensageiro/genética
9.
Mol Plant Microbe Interact ; 34(7): 852-856, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33656373

RESUMO

Venturia carpophila, the causal agent of scab disease on peach, is a host-specific fungus that is widely distributed around the world, including China. In our previous study, samples were collected from 14 provinces in China, and 750 isolates were obtained by single-spore separation. Here, we reported the first highly contiguous whole-genome sequence (35.87 Mb) of the V. carpophila isolate ZJHZ1-1-1, which included 33 contigs with N50 value of 2.01 Mb and maximum contig length of 3.39 Mb. The high-quality genome sequence and annotation resource will be useful to study the fungal biology, pathogen-host interaction, fungicide resistance, characterization of important genes, population genetic diversity, and development of molecular markers for genotyping and species identification.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Prunus persica , Fungos do Gênero Venturia , Genoma Fúngico/genética , Doenças das Plantas , Prunus persica/genética
10.
Physiol Mol Biol Plants ; 26(2): 379-389, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32158142

RESUMO

In order to ascertain the regulatory mechanism of fruit development in Isatis indigotica Fortune, the complementary DNA (cDNA) sequence of the SHATTERPROOF 2 (SHP2) orthologous gene was identified by Rapid Amplification of cDNA Ends technology and the corresponding gene was named IiSHP2. The expression pattern of IiSHP2 was determined by quantitative reverse transcription-polymerase chain reaction and wild-type Col-0 Arabidopsis plants were transformed with the IiSHP2 gene using Agrobacterium tumefaciens and the floral-dip method. Expression analyses indicated that IiSHP2 was highly expressed in flowers, silicles and seeds. Compared to wild-type plants, IiSHP2 transgenic lines bolted earlier. Detailed phenotypic observations showed that the size of the rosette and cauline leaves in transgenic lines was reduced and the cauline leaves of the transgenic lines were incurved and displayed a funnel-like shape. During the reproductive growth stage, IiSHP2 transgenic plants produced shortened sepals and the flower buds were not encapsulated completely. Moreover, the petals of the transgenic lines were converted into stamineous tissues, accompanied by exposed stamens, short malformed siliques and wrinkled valves, indicating a severe decline in fertility. These experimental conclusions are valuable as a reference for the breeding of medicinal plants.

11.
J Cell Biochem ; 119(11): 9573-9582, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30129150

RESUMO

Colorectal cancer remains a leading malignancy in humans. The importance of epigenetic modification in the development of this disease is now being recognized. The reversible and dynamic nature of epigenetic modifications provides a promising strategy in colorectal cancer chemoprevention and treatment. Luteolin (LUT), a flavone dietary phytochemical, can modulate various signaling pathways involved in carcinogenesis. Many studies have demonstrated that LUT inhibits colorectal carcinogenesis by activating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-responsive element (ARE) pathway. However, the potential epigenetic mechanism underlying Nrf2/ARE pathway activation remains unclear. In this study, we aimed to explore the anticancer potential of LUT in human colon cancer cells and the epigenetic regulation of the Nrf2/ARE pathway. Specifically, our data showed that LUT suppressed cell proliferation and cellular transformation of HCT116 and HT29 cells in a dose-dependent manner. Additionally, quantitative real-time polymerase chain reaction and Western blot analysis were performed to determine the mRNA and protein expression of Nrf2 and its downstream genes after LUT treatment. Bisulfite genomic sequencing revealed that methylation of the Nrf2 promoter region was decreased by LUT, corresponding with the increased mRNA expression of Nrf2. Decreased protein levels and enzyme activities of epigenetic modifying enzymes, such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), were also observed in LUT-treated HCT116 cells. In summary, our findings suggest that LUT may exert its antitumor activity in part via epigenetic modifications of the Nrf2 gene with subsequent induction of its downstream antioxidative stress pathway.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Epigênese Genética/genética , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Epigênese Genética/efeitos dos fármacos , Células HCT116 , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
12.
Cancer Sci ; 109(5): 1393-1403, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29569792

RESUMO

Gastric cancer (GC) is among the most fatal cancers in China. MicroRNAs (miRNAs) are versatile regulators during GC development and progression. miR-491-5p has been demonstrated to act as a tumor suppressor in several types of cancer. However, the role of miR-491-5p in GC metastasis remains unknown. Here, we found that miR-491-5p was significantly decreased in GC tissues compared with adjacent non-cancerous tissues, and low miR-491-5p level was associated with large tumor size. Overexpression of miR-491-5p significantly suppressed GC cell epithelial-to-mesenchymal transition (EMT) and tumor metastasis in vitro and in vivo. Mechanistically, SNAIL was identified as a direct target of miR-491-5p. The silencing of SNAIL phenocopied the tumor suppressive function of miR-491-5p, whereas re-expression of SNAIL in GC cells rescued the EMT markers and cell migratory ability that were inhibited by miR-491-5p. In addition, miR-491-5p inhibited FGFR4 indirectly. Inhibition of FGFR4 also decreased the SNAIL level and impaired EMT and cell migration. Taken together, these findings indicate that downregulation of miR-491-5p promoted GC metastasis by inducing EMT via regulation of SNAIL and FGFR4.


Assuntos
MicroRNAs/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição da Família Snail/genética , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Carga Tumoral
13.
Clin Immunol ; 194: 1-8, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29906512

RESUMO

Increasing rates of life-threatening infections and decreasing susceptibility to antibiotics urge an effective vaccine targeting Staphylococcus aureus. Here we investigate the role of cellular immunity in FnBPA110-263 mediated protection in Staphylococcus aureus infection. This study revealed FnBPA110-263 broadly protected mice from seven FnBPA isotypes strains in the sepsis model. FnBPA110-263 immunized B-cell deficient mice were protected against lethal challenge, while T-cell deficient mice were not. Reconstituting mice with FnBPA110-263 specific CD4+ T-cells conferred antigen specific protection. In vitro assays indicated that isolated FnBPA110-263 specific splenocytes from immunized mice produced abundant IL-17A. IL-17A deficient mice were not protected from a lethal challenge by FnBPA110-263 vaccination. Moreover, neutralizing IL-17A, but not IFN-γ,reverses FnBPA110-263-induced protective efficacy in sepsis and skin infection model. These findings suggest that IL-17A producing Th17 cells play an essential role in FnBPA110-263 vaccine-mediated defense against S. aureus sepsis and skin infection in mice.


Assuntos
Adesinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Sepse/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Imunidade Celular/imunologia , Interferon gama/imunologia , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos SCID , Sepse/microbiologia , Células Th17/imunologia , Células Th17/microbiologia , Vacinação/métodos
14.
Biochem Biophys Res Commun ; 502(2): 283-288, 2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29842883

RESUMO

TSP50, a testis-specific gene encoding a serine protease-like protein, was specifically expressed in the spermatocytes of testes but abnormally activated and expressed in many different kinds of cancers. Here, we aimed to analyze the expression of TSP50 in mouse embryo and its function in early embryonic development. Firstly, the distribution of TSP50 in oocytes and embryonic development was characterized by immunofluorescence, RT-PCR and western blotting, and the results showed that TSP50 was detected at all studied stages with a dynamic expression pattern. When overexpressed TSP50 in zygotes by microinjection, the zygotes development was highly accelerated. On the contrary, knocking down TSP50 expression by RNA interference greatly retarded the zygote development. Furthermore, TSP50 expression at embryonic day 6.5 (E6.5), day 8.5 (E8.5) and day 10.5 (E10.5) were increasingly enhanced, However, the expression of TSP50 decreased gradually in the development and differentiation of cardiac myocyte from E12.5 to postnatal (P0). Additionally, we found that TSP50 expression was decreased during cardiac myocyte differentiation of P19 cells. Overexpression of TSP50 could decrease the expression of GATA-4, and knockdown of TSP50 markedly increase the expression of GATA-4. Taken together, our data indicate that TSP50 may play an important role during the process of mouse embryonic development as well as myocardial cell differentiation.


Assuntos
Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/fisiologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/enzimologia , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Coração Fetal/embriologia , Coração Fetal/enzimologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Gravidez
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(9): 1076-1081, 2016 Sep.
Artigo em Zh | MEDLINE | ID: mdl-30645846

RESUMO

Objective To preliminarily observe miRNA gene profiles in benefit serum of advanced non-small cell lung cancer (NSCLC) treated by TCM combined Western medicine (WM) , and to seek for molecular markers for its efficacy monitoring and prediction. Methods Recruited were 5 advanced NSCLC patients who received TCM combined WM treatment and obtained efficacy benefit ( as the treatment group) , 3 advanced NSCLC patients who received early treatment ( as the lung cancer group) , and 3 healthy subjects (as the control group). Serum samples were collected and total RNA was extracted using Trizol method. Using microRNA PCR ARRAY chip technology (product of Exiqon Company) , differentially miRNA expression profiling in serum between the lung cancer group and the control group, and between the treatment group and the lung cancer group were detected. Benefit miRNA expression profiling was ob- tained based on cluster analysis and comparative analysis. Results After tested by miRNA PCR ARRAY and managed by data analysis, a total of 42 miRNAs with more than 2 folds difference were screened in the lung cancer group and the control group, including 29 up-regulated and 12 down-regulated miRNAs. Be- sides, miR-10b-5p, miR-21-5p, miR-182-5p, miR-361-3p, and miR-382-5p were statistically different (P < 0. 05). A total of 45 miRNAs with more than 2 folds difference were screened in the treatment group and the lung cancer group, including 12 up-regulated and 33 down-regulated miRNAs. Fifteen miRNAs were statistically different including miR-137-3p, miR-182-5p, miR-376a-3p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-29a-3p, miR-141-3p, miR-150-5p, miR-200c-3p, miR-342-3p, miR-365a-3p, miR-375, miR- 502-3p (P<0.05). Totally 22 miRNAs were screened in the treatment group with more than 2 folds differ- ence as compared with the lung cancer group and with less than or equivalent to 2 folds difference as com- pared with the control group, including 7 up-regulated and 15 down-regulated miRNAs, of which, miR-127- 3p, miR-182-5p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-141-3p, miR-342-3p were statistically different (P <0. 05). Conclusion miRNAs including miR-21-5p, miR-182-5p, miR-382-5p are promising to become molecular markers for efficacy monitoring and prediction of advanced NSCLC treated by TCM combined WM, which provides reference for individualized treating advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Medicina Tradicional Chinesa , MicroRNAs , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/terapia , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos
17.
Zhongguo Zhong Yao Za Zhi ; 41(23): 4389-4392, 2016 Dec.
Artigo em Zh | MEDLINE | ID: mdl-28933117

RESUMO

The phytochemistry investigation on the Cassia occidentalis, a Dai Medicine, was carried out. The C. occidentalis was extracted with ethanol and then partitioned with EtOAc. The EtOAc soluble materials were subjected repeatedly to column chromatography on silica gel and preparative RP-HPLC, leading to isolation of a nor-sesquiterpene, 3-isopropyl-1,6-dimethoxy-5-methyl-naphthalen-7-ol (1), and a sesquiterpene, 2,7-dihydroxy-4-isopropyl-6-methyl-naphthalene-1-carbaldehyde (2). Their structures were determined by means of spectroscopic studies. Compound 1 is a new compound. Compound 2 is also isolated from C. occidentalis for the first time. In addition, the cytotoxicity of compound 1 for NB4, A549, SHSY5Y, PC3, and MCF7 cells line was assayed by using the MTT method, and it displayed potential cytotoxicity for the tested cancer cell-line with IC50 valves of (1.8±0.2), (1.2±0.2), (0.9±0.1), (2.2±0.3), (2.6±0.3) µmol•L⁻¹, respectively.


Assuntos
Senna/química , Sesquiterpenos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Sesquiterpenos/farmacologia
18.
Gut ; 64(9): 1368-78, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25134787

RESUMO

OBJECTIVE: Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. DESIGN: Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. RESULTS: Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis.


Assuntos
Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Mediadores da Inflamação/metabolismo , Interleucinas/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Biomarcadores/metabolismo , Células Cultivadas , Quimiocina CXCL2/imunologia , Quimiocina CXCL2/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Gastrite/imunologia , Gastrite/fisiopatologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/patogenicidade , Humanos , Mediadores da Inflamação/imunologia , Interleucinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Papel (figurativo) , Sensibilidade e Especificidade , Linfócitos T Auxiliares-Indutores/metabolismo , Transfecção , Interleucina 22
19.
Org Lett ; 26(25): 5274-5279, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38885640

RESUMO

Chiral α-aminophosphonates with adjacent carbon and phosphonate stereogenic centers have been employed as ligands in the copper-catalyzed oxidative coupling of 2-naphthols, resulting in the production of chiral BINOLs in favorable yields and moderate to good enantiomeric excess. This represents the first application of chiral P-based ligands to enable such a transformation. The synthesis of these chiral α-aminophosphonate ligands offers a significant advantage over approaches that typically necessitate elaborate synthetic processes for chiral ligand production.

20.
Chin J Integr Med ; 30(4): 366-378, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38212503

RESUMO

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor, with active ingredients of bufadienolides and indole alkaloids. With further research and clinical applications, it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells, promoting apoptosis, inhibiting formation of tumor neovascularization, reversing multidrug resistance, and regulating immune response; it also has the functions of relieving cancer pain and regulating immune function. In this paper, the chemical composition, pharmacological effects, clinical applications, and adverse reactions of cinobufacini are summarized. However, the extraction of monomer components of cinobufacini, the relationship between different mechanisms, and the causes of adverse reactions need to be further studied. Also, high-quality clinical studies should be conducted.


Assuntos
Venenos de Anfíbios , Bufanolídeos , Neoplasias , Animais , Humanos , Neoplasias/tratamento farmacológico , Bufonidae , Venenos de Anfíbios/farmacologia , Venenos de Anfíbios/uso terapêutico , Venenos de Anfíbios/química , Bufanolídeos/farmacologia , Bufanolídeos/uso terapêutico
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